gebhart/patrepeval huggingface dataset:
Free radical scavenging: a potentially beneficial action of thiol-containing angiotensin converting enzyme inhibitors (1990)

Free radical (FR) scavenging may be a therapeutically useful adjunctive property of angiotensin converting enzyme (ACE) inhibitors. In this study we have shown that SH-containing ACE inhibitors (captopril, epicaptopril, zofenopril) are potent FR scavengers at a concentration of 4 x 10(-5) M whereas non-SH ACE inhibitors (enalaprilat, quinaprilat and perindoprilat) have no FR-scavenging activity at this concentration. Furthermore, the SH-containing agents preferentially scavenged general radicals rather than superoxide radicals, i.e. suggesting that these drugs would be effective in quenching the culprit FR in ischaemia/reperfusion injury.
Direct Fluorescence Monitoring of the Delivery and Cellular Uptake of a Cancer-Targeted RGD Peptide-Appended Naphthalimide Theragnostic Prodrug (2012)

Presented here is a multicomponent synthetic strategy that allows for the direct, fluorescence-based monitoring of the targeted cellular uptake and release of a conjugated therapeutic agent. Specifically, we report here the design, synthesis, spectroscopic characterization, and preliminary in vitro biological evaluation of a RGD peptide-appended naphthalimide pro-CPT (compound 1). Compound 1 is a multifunctional molecule composed of a disulfide bond as a cleavable linker, a naphthalimide moiety as a fluorescent reporter, an RGD cyclic peptide as a cancer-targeting unit, and camptothecin (CPT) as a model active agent. Upon reaction with free thiols in aqueous media at pH 7.4, disulfide cleavage occurs. This leads to release of the free CPT active agent, as well as the production of a red-shifted fluorescence emission (λ(max) = 535 nm). Confocal microscopic experiments reveal that 1 is preferentially taken up by U87 cells over C6 cells. On the basis of competition experiments involving okadaic acid, an inhibitor of endocytosis, it is concluded that uptake takes place via RGD-dependent endocytosis mechanisms. In U87 cells, the active CPT payload is released within the endoplasmic reticulum, as inferred from fluorescence-based colocalization studies using a known endoplasmic reticulum-selective dye. The present drug delivery system (DDS) could represent a new approach to so-called theragnostic agent development, wherein both a therapeutic effect and drug uptake-related imaging information are produced and can be readily monitored at the subcellular level. In due course, the strategy embodied in conjugate 1 could allow for more precise monitoring of dosage levels, as well as an improved understanding of cellular uptake and release mechanisms.
Notch signaling in vascular morphogenesis (2004)

An emerging hallmark of the Notch signaling pathway is its nearly ubiquitous participation in cell fate decisions that affect several tissues, including epithelial, neuronal, hematopoietic, and muscle. The vascular compartment has been the latest addition to the list of tissues known to be regulated by Notch. Unraveling the contribution of Notch signaling to blood vessel formation has resulted principally from gain-of-function and loss-of-function experiments in mouse and zebrafish. During the past 4 years, these mechanistic studies have revealed that Notch is required for the successful completion of several steps during vascular morphogenesis and differentiation. In addition, the findings that Notch mutations are linked to some late-onset hereditary vascular pathologic conditions suggest the added contribution of this signaling pathway to vascular homeostasis.
Study on the feasibility of micro camera systems for asynchronous, gigantic satellite constellation (2019)

In this paper, a development approach is proposed for micro-camera systems that are dedicated to constellation operations of satellites. It is to take a regular practice and design the system based on traditional, professional optical layouts rather than simplifying configuration. LIBERO-1 and LIBERO-2 are the cameras under development to study whether the approach is feasible. LIBERO-1 is designed to have better than 1-m resolution in panchromatic spectral channel at the altitude of 500 km. It can support up to 6 multispectral channels and 12000 active pixels in swathwidth. The dimension is estimated to be within 20 cm x 20 cm x 30 cm, which is almost half the length of 1-m resolution cameras available in market. LIBERO-2 has better than 2-m resolution at 500 km altitude. It can also support up to 6 multispectral channels and 8000 active pixels in swathwidth. LIBERO-2 has a similar size to star sensors so that its dimension is 10 cm x 10 cm x 20 cm.
Cecil Textbook of Medicine (1988)

cecil text book of medicine , cecil text book of medicine , کتابخانه الکترونیک و دیجیتال - آذرسا
A No-Reference Objective Image Sharpness Metric Based on Just-Noticeable Blur and Probability Summation (2007)

This work presents a perceptual-based no-reference objective image sharpness/blurriness metric by integrating the concept of just noticeable blur (JNB) into a probability summation model. Unlike existing objective no-reference image sharpness/blurriness metrics, the proposed metric is able to predict the relative amount of blurriness in images with different content. Results are provided to illustrate the performance of the proposed perceptual-based sharpness metric. These results show that the proposed sharpness metric correlates well with the perceived sharpness.
vacB, a novel chromosomal gene required for expression of virulence genes on the large plasmid of Shigella flexneri (1992)

Shigellae, the causative agents of bacillary dysentery, are capable of adhering to and invading epithelial cells and spreading into adjacent cells. A chromosomal mutant of Shigella flexneri 2a YSH6000 with reduced invasive capacity was isolated by Tn5 insertion mutagenesis. The linkage of the mutant phenotype to the Tn5 insertion was determined by P1 phage transduction. The site of the Tn5 insertion was assigned to a NotI chromosomal restriction map, confirming that the virulence-associated locus, designated vacB, is a new locus on the chromosome. In the vacB mutant, production of the four plasmid-encoded virulence antigens, IpaB, -C, and -D and VirG, decreased to a low level compared with that in the wild type. In contrast, levels of transcription of the operons for virG, ipa, region-3.4, region-5, virF, and virB on the large plasmid, as determined by Northern dot blotting, were unaffected in the vacB mutant. Furthermore, transcriptional activation of the ipa operon by exploiting a tac promoter could not restore the vacB mutant to production of the same levels of the IpaB, -C, and -D proteins as those in the wild type, indicating that the vacB locus is involved in expression of the vir genes on the large plasmid at the posttranscriptional level. Cloning followed by nucleotide sequencing of the vacB region showed it to contain a 2,280-bp open reading frame encoding an 86.9-kDa protein located 669 bp downstream from the 3' end of the open reading frame for the purA gene. Disruption of the vacB gene of other serotypes of Shigella spp. and enteroinvasive Escherichia coli (EIEC) resulted in reduced expression of virulence phenotypes, indicating that the vacB gene encodes a novel type of virulence-associated gene required for the full expression of the virulence phenotype of Shigella spp. and EIEC.
Fundamentals of Statistical Signal Processing: Estimation Theory (1995)

"Fundamentals of Statistical Signal Processing: Estimation Theory." Technometrics, 37(4), pp. 465–466
Future optical fiber transmission technology and networks (1988)

The authors contend that optical system developments, which so far have followed a straightforward and logical path from direct link replacement to the proposed transwitching networks, will evolve towards passive (fiber-only) networks that could ultimately see the eradication of the central office. To explain this view of the future, they briefly trace optical system developments to the present day before citing the technology developments that have led them to the conclusion. They discuss present network and technology trends, focusing on the reduction of the amount of electronic hardware, the disappearance of bandwidth efficiency as an important factor, and the state of the optical network today. They then turn to the future network and technology, showing how the central office can be dispensed with by operating the network on a radio mode, with each terminal assigned a specific frequency.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Kaposi's Sarcoma–Associated Herpesvirus-Like DNA Sequences in AIDS-Related Body-Cavity–Based Lymphomas (1995)

The recently discovered KSHV DNA sequences occur in an unusual subgroup of AIDS-related B-cell lymphomas, but not in any other lymphoid neoplasm studied thus far. Our finding strongly suggests that a novel herpesvirus has a pathogenic role in AIDS-related body-cavity-based lymphomas.
Characterization of an ATP-Dependent DNA Strand Transferase from Human Cells (1987)

We have characterized an enzymatic activity from human cell nuclei which is capable of catalyzing strand exchange between homologous DNA sequences. The strand exchange activity was Mg2+ dependent and required ATP hydrolysis. In addition, it was capable of promoting reannealing of homologous DNA sequences and could form nucleoprotein networks in a fashion reminiscent of purified bacterial RecA protein. Using an in vitro recombination assay, we also showed that the strand exchange activity was biologically important. The factor(s) responsible for the activity has been partially purified.
Utilizing the BiTE (bispecific T-cell engager) platform for immunotherapy of cancer (2015)

Various approaches of T-cell-based cancer immunotherapy are currently under investigation, among these are BiTE® (bispecific T-cell engager) antibody constructs, which have a unique design and mechanism of action. They are constructed by genetically linking onto a single polypeptide chain the minimal binding domains of monoclonal antibodies for tumor-associated surface antigens and for the T-cell receptor-associated molecule CD3. Concurrent engagement of the target cell antigen and CD3 leads to activation of polyclonal cytotoxic T-cells, resulting in target cell lysis. Blinatumomab, a BiTE targeting CD19, is being investigated in a broad range of B-cell malignancies and has recently been approved in the USA by the US FDA for Philadelphia chromosome-negative relapsed/refractory B-acute lymphoblastic leukemia under the trade name BLINCYTO™. The BiTE platform is one of the clinically most advanced T-cell immunotherapy options.
The nucleotide sequence of the 5′ and 3′ ends of rota virus SA11 gene 4 (1987)

Journal Article The nucleotide sequence of the 5′ and 3′ ends of rota virus SA11 gene 4 Get access Susana López, Susana López * Departamento de Biologia Molecular, Institute de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoMexico City 04510, México * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Carlos F. Arias Carlos F. Arias Departamento de Biologia Molecular, Institute de Investigaciones Biomédicas, Universidad Nacional Autónoma de MéxicoMexico City 04510, México Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 15, Issue 11, 11 June 1987, Page 4691, https://doi.org/10.1093/nar/15.11.4691 Published: 11 June 1987 Article history Received: 27 April 1987 Published: 11 June 1987
Identification of CD4+ T Cell Epitopes from NY-ESO-1 Presented by HLA-DR Molecules (2000)

In previous studies, the shared cancer-testis Ag, NY-ESO-1, was demonstrated to be recognized by both Abs and CD8+ T cells. Gene expression of NY-ESO-1 was detected in many tumor types, including melanoma, breast, and lung cancers, but was not found in normal tissues, with the exception of testis. In this study, we describe the identification of MHC class II-restricted T cell epitopes from NY-ESO-1. Candidate CD4+ T cell peptides were first identified using HLA-DR4 transgenic mice immunized with the NY-ESO-1 protein. NY-ESO-1-specific CD4+ T cells were then generated from PBMC of a patient with melanoma stimulated with the candidate peptides in vitro. These CD4+ T cells recognized NY-ESO-1 peptides or protein pulsed on HLA-DR4+ EBV B cells, and also recognized tumor cells expressing HLA-DR4 and NY-ESO-1. A 10-mer peptide (VLLKEFTVSG) was recognized by CD4+ T cells. These studies provide new opportunities for developing more effective vaccine strategies by using tumor-specific CD4+ T cells. This approach may be applicable to the identification of CD4+ T cell epitopes from many known tumor Ags recognized by CD8+ T cells.
Branhamella catarrhalis: an organism gaining respect as a pathogen (1990)

Branhamella catarrhalis was formerly regarded as a common, essentially harmless inhabitant of the pharynx. This misapprehension was caused, in part, by confusion with another pharyngeal resident, Neisseria cinerea. The two organisms can now be differentiated by the positive reactions of B. catarrhalis in tests for nitrate reduction and hydrolysis of tributyrin and DNase. B. catarrhalis is currently recognized as the third most frequent cause of acute otitis media and acute sinusitis in young children. It often causes acute exacerbations of chronic bronchopulmonary disease in older or immunocompromised adults and is incriminated occasionally in meningitis, endocarditis, bacteremia, conjunctivitis, keratitis, and urogenital infections. Virulence-associated factors, such as pili, capsules, outer membrane vesicles, iron acquisition proteins, histamine-synthesizing ability, resistance to the bactericidal action of normal human serum, and binding to the C1q complement component, have been identified in some strains. beta-Lactamase producing strains, first detected in 1976, have risen to approximately 75% worldwide. Thus far, however, practically all American strains of B. catarrhalis remain susceptible to alternative antibiotics. A possible selective advantage of recent isolates is their reportedly heightened tendency for adherence to oropharyngeal cells from patients with chronic bronchopulmonary disease.
Communication Requirements and Network Design for IVHS (1993)

This paper presents the communication needs between vehicles and the roadside infrastructure for IVHS applications. The requirements of each application, in terms of message length, frequency, and acceptable delay, are estimated. Based on these estimates, we assess the amount of radio spectrum needed to support these applications. We find that about 1.2 MHz is required to support full highway coverage. We discuss the topology and capacity allocation problems for the road-based network and present one possible implementation. We show a case study of network design and link capacity calculation for the San Francisco Bay Area highway system, as an illustration of the proposed solution. The results provide an indication for the communication media suitable for the network.
A Simplified Approach to Common Stock Valuation (1985)

As the quest for above-average returns becomes ever more competitive, efficient utilization of resources in money management firms becomes increasingly important. A valuation model derived from the two-stage dividend discount model, but using approximations based on fundamental investment principles, can add efficiency and value by focusing investment resources on those companies that are most likely to offer superior returns in the future. Analysis of the model using ex post data indicates that it can successfully identify the important factors that differentiate superior from inferior performance. The model simplifies the investment process by focusing on two of the most important components in determination of future stock price-earnings growth and price-earnings ratio. Preliminary tests using ex ante data suggest that superior performance at lower or comparable risk levels is achieved from a strategy of purchasing stocks assigned high valuation numbers by the model and avoiding those with low valuation numbers.
In vitro establishment and characterization of a human megakaryoblastic cell line (1990)

A human megakaryoblastic cell line, designated CHRF-288-11, has been established in vitro through the use of adherent stromal cells in long-term human bone marrow culture. Long-term bone marrow cultures were required for the initial adaptation of the megakaryoblastic cells to culture conditions; however, once adapted, the cells were weaned from the stromal layer until they proliferated in the complete absence of any feeder layers. The seed cells for the establishment of this line were derived from a solid tumor; the cloned cell line derived from this tumor exhibits markers characteristic of megakaryocytes and platelets. Specifically, the cells express platelet peroxidase, platelet factor 4, and platelet Ca+(+)-adenosine triphosphatase (ATPase), glycoprotein IIb-IIIa (CDw41), factor VIII antigen, and the MY7 (CD13) and MY9 (CD33) antigens. The cells do not express the erythroid markers glycophorin A and hemoglobin, the myeloid marker myeloperoxidase, nor markers specific for T and/or B cells. The established cell line produces both basic fibroblast growth factor and transforming growth factor-beta, properties demonstrated previously for the solid tumor. The clonal cell population exhibited a unique, singular karyotype, indicating cellular homogeneity. The cells display a doubling time of approximately 33 hours in either 25% horse or calf serum. Treatment of the cells with 1 X 10(-8) mol/L phorbol 12-myristate 13-acetate (PMA) leads to the induction of multi-nucleation and hyperploidy in the cells, with approximately 35% of the cells exhibiting two or more nuclei per cell, and greater than 80% of the cells enlarging in size. The establishment of this unique cell line under defined culture conditions will be beneficial for the future study of megakaryocytic properties expressed by this cell line.
Overexpression of manganese superoxide dismutase attenuates neuronal death in human cells expressing mutant (G37R) Cu/Zn‐superoxide dismutase (2002)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of motor function and eventual death as a result of degeneration of motor neurons in the spinal cord and brain. The discovery of mutations in SOD1, the gene encoding the antioxidant enzyme Cu/Zn-superoxide dismutase (CuZnSOD), in a subset of ALS patients has led to new insight into the pathophysiology of ALS. Utilizing a novel adenovirus gene delivery system, our laboratory has developed a human cell culture model using chemically differentiated neuroblastoma cells to investigate how mutations in SOD1 lead to neuronal death. Expression of mutant SOD1 (G37R) resulted in a time and dose-related death of differentiated neuroblastoma cells. This cell death was inhibited by overexpression of the antioxidant enzyme manganese superoxide dismutase (MnSOD). These observations support the hypothesis that mutant SOD1-associated neuronal death is associated with alterations in oxidative stress, and since MnSOD is a mitochondrial enzyme, suggest that mitochondria play a key role in disease pathogenesis. Our findings in this model of inhibition of mutant SOD1-associated death by MnSOD represent an unique approach to explore the underlying mechanisms of mutant SOD1 cytotoxicity and can be used to identify potential therapeutic agents for further testing.
Discovery of HDAC Inhibitors That Lack an Active Site Zn2+-Binding Functional Group (2012)

Natural and synthetic histone deacetylase (HDAC) inhibitors generally derive their strong binding affinity and high potency from a key functional group that binds to the Zn(2+) ion within the enzyme active site. However, this feature is also thought to carry the potential liability of undesirable off-target interactions with other metalloenzymes. As a step toward mitigating this issue, here, we describe the design, synthesis, and structure-activity characterizations of cyclic α3β-tetrapeptide HDAC inhibitors that lack the presumed indispensable Zn(2+)-binding group. The lead compounds (e.g., 15 and 26) display good potency against class 1 HDACs and are active in tissue culture against various human cancer cell lines. Importantly, enzymological analysis of 26 indicates that the cyclic α3β-tetrapeptide is a fast-on/off competitive inhibitor of HDACs 1-3 with K i values of 49, 33, and 37 nM, respectively. Our proof of principle study supports the idea that novel classes of HDAC inhibitors, which interact at the active-site opening, but not with the active site Zn(2+), can have potential in drug design.
Host cell protein dynamics in the supernatant of a mAb producing CHO cell line (2011)

The characterization of host cell protein (HCP) content during the production of therapeutic recombinant proteins is an important aspect in the drug development process. Despite this, key components of the HCP profile and how this changes with processing has not been fully investigated. Here we have investigated the supernatant HCP profile at different times throughout culture of a null and model GS-CHO monoclonal antibody producing mammalian cell line grown in fed-batch mode. Using 2D-PAGE and LC-MS/MS we identify a number of intracellular proteins (e.g., protein disulfide isomerise; elongation factor 2; calreticulin) that show a significant change in abundance relative to the general increase in HCP concentration observed with progression of culture. Those HCPs that showed a significant change in abundance across the culture above the general increase were dependent on the cell line examined. Further, our data suggests that the majority of HCPs in the supernatant of the cell lines investigated here arise through lysis or breakage of cells, associated with loss in viability, and are not present due to the secretion of protein material from within the cell. SELDI-TOF and principal components analysis were also investigated to enable rapid monitoring of changes in the HCP profile. SELDI-TOF analysis showed the same trends in the HCP profile as observed by 2D-PAGE analysis and highlighted biomarkers that could be used for process monitoring. These data further our understanding of the relationship between the HCP profile and cell viability and may ultimately enable a more directed development of purification strategies and the development of cell lines based upon their HCP profile.
The thiol-activated toxin streptolysin O does not require a thiol group for cytolytic activity (1989)

Site-directed mutagenesis of the TGC codon in a cloned streptolysin O (SLO) gene exchanged the single Cys residue in SLO for either Ala or Ser. The parent wild-type SLO (SLO.Cys-530) and the SLO.Ala-530 and SLO.Ser-530 mutant toxins, expressed in Escherichia coli, were purified and analyzed. Wild-type SLO.Cys-530 and the SLO.Ala-530 mutant showed no significant differences in their specific hemolytic activities, while the SLO.Ser-530 mutant had a reduced (ca. 25%), but still considerable, specific hemolytic activity as compared with that of wild-type SLO. The parent and mutant toxins extracted from lysed erythrocyte membranes had similar sedimentation profiles on sucrose density gradients, suggesting that the mutations did not affect the ability of SLO to form oligomers in membranes. These results show that the widely held assumption that the in vitro cytolytic activity of SLO requires an essential Cys residue is not true.