gebhart/patrepeval huggingface dataset:
Thrombospondin binding to specific sequences within the A alpha- and B beta-chains of fibrinogen. (1990)

Thrombospondin is a multifunctional adhesive glycoprotein which binds to the surface of resting and activated platelets. Thrombospondin also binds to a variety of proteins, including fibrinogen. The interactions between platelet-bound thrombospondin and fibrinogen are thought to facilitate irreversible platelet aggregation. Both the A alpha- and B beta-chains of fibrinogen specifically bind to thrombospondin. Cyanogen bromide cleavage products of the fibrinogen A alpha- and B beta-chains, and synthetic peptides corresponding to specific regions of these cleavage products were utilized to identify the regions of the fibrinogen A alpha- and B beta-chains which bind to thrombospondin. Cyanogen bromide fragments of the A alpha- and B beta-fibrinogen chains, resolved by gel filtration and reversed-phase chromatography, were examined for thrombospondin binding activity. Thrombospondin specifically bound to the A alpha-chain fragment encompassing residues 92-147 and the B beta-chain fragment encompassing residues 243-305. Analyses of the binding characteristics of two series of overlapping synthetic peptides revealed that peptides corresponding to residues 113-126 of the A alpha-chain and residues 243-252 of the B beta-chain retained thrombospondin binding activity. Separate bovine serum albumin conjugates of the active A alpha-chain and B beta-chain peptides inhibited platelet aggregation. These studies reveal that fibrinogen possesses at least two unique sequences which are recognized by thrombospondin and that such interaction may affect platelet aggregation.
Insight into the Mechanism of the Asymmetric Addition of Alkyl Groups to Aldehydes Catalyzed by Titanium−BINOLate Species (2002)

The asymmetric addition of alkyl groups to aldehydes catalyzed by BINOLate-titanium complexes has become the testing grounds to evaluate the potential of new BINOL-based ligands. We have investigated the mechanism of this reaction and report our findings here. Model systems for the open form of the catalyst, (BINOLate)[Ti(O-i-Pr)(3)](2), based on mono-oxygen-alkylated BINOL ligands have been examined. Comparison of the reactivity and enantioselectivity of the mono-alkyl BINOL derivatives with those of BINOL indicate that the open form of the catalyst, (BINOLate)[Ti(O-i-Pr)(3)](2), is not active in the asymmetric addition reaction. Several BINOLate-titanium complexes have been synthesized and characterized by X-ray crystallography. These include the dinuclear (BINOLate)Ti(O-i-Pr)(2).Ti(O-i-Pr)(4), which contains a bridging naphtholate and isopropoxy group, trinuclear (BINOLate)Ti(O-i-Pr)(2).[Ti(O-i-Pr)(4)](2), and trimeric [(BINOL)Ti(O-i-Pr)(2)](3). The solid-state and solution structures reported here indicate that (BINOLate)Ti(O-i-Pr)(2) prefers to bind to titanium tetraisopropoxide rather than to itself, explaining why no nonlinear effects are observed in the catalytic reaction. Additionally, experimental evidence suggests that the BINOLate-titanium species responsible for the catalytic and stoichiometric asymmetric addition reactions are different, indicating that the proposed intermediate, (BINOLate)Ti(R)(aldehyde)(O-i-Pr), is not involved in either of these processes. Reactions were examined using different sources of the alkyl group [ZnMe(2) or MeTi(O-i-Pr)(3)]. Under similar conditions, it was found that the product ee's were the same, independent of whether ZnMe(2) or Me-Ti(O-i-Pr)(3) was used as the source of the alkyl groups. This indicates that the role of the dialkylzinc is not to add the alkyl group to the carbonyl but rather to transfer the alkyl group to titanium. On the basis of these results, we hypothesize that the intermediate in the asymmetric addition involves (BINOLate)Ti(O-i-Pr)(2)(aldehyde).MeTi(O-i-Pr)(3).
Synthesis of an end-group functionalized polyethylene glycol-lipid conjugate for preparation of polymer-grafted liposomes (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of an end-group functionalized polyethylene glycol-lipid conjugate for preparation of polymer-grafted liposomesSamuel ZalipskyCite this: Bioconjugate Chem. 1993, 4, 4, 296–299Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://pubs.acs.org/doi/10.1021/bc00022a008https://doi.org/10.1021/bc00022a008research-articleACS PublicationsRequest reuse permissionsArticle Views3355Altmetric-Citations112LEARN 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
Inhibition of insulin-like growth factor I receptor increases the antitumor activity of doxorubicin and vincristine against Ewing's sarcoma cells. (2001)

Innovative treatment modalities are needed for Ewing's sarcoma (ES), a neoplasm with a disappointingly low survival rate despite the use of aggressive multimodal therapeutic approaches. We and others (D. Yee et al., J. Clin. Investig., 86: 1806-1814, 1990; K. Scotlandi et al., Cancer Res., 56: 4570-4574, 1996) have previously shown the existence and the pathogenetic relevance of an autocrine loop, mediated by the insulin-like growth factor-I receptor (IGF-IR), which is crucial for survival and proliferation of ES cells in vitro. Moreover, we reported that the IGF-IR-blocking monoclonal antibody (MAb), alphaIR3, as well as suramin, a drug that can interfere with growth factor by binding to the receptors, inhibited both the tumorigenic and the metastatic ability of ES cells in athymic mice. In this study, we analyzed whether agents that can block the IGF-IR-mediated loop are of value in association with conventional cytotoxic drugs for the design of more effective therapeutic regimens. Both alphaIR3 MAb and suramin treatment significantly increased the antitumor in vitro effects of doxorubicin and vincristine, two drugs with a leader action on ES. These findings were obtained by both simultaneous and sequential treatments. Analysis of the proliferation rate and of apoptosis revealed that alphaIR3 MAb and suramin significantly enhanced the G(1)-phase rate induced by doxorubicin, without substantially affecting doxorubicin-G(2)-M-blockage of cell cycle, and significantly increased the induction of apoptosis, which confirmed that the specific blockage of IGF-IR deprives ES cells of an important tool for the prevention of drug-induced apoptosis. Moreover, combination treatments of doxorubicin plus alphaIR3 MAb significantly increase the doxorubicin-induced impairment of the ability of ES cells to form colonies in soft agar. In conclusion, we showed that, in ES, the blockage of IGF-IR by a neutralizing MAb or by suramin may greatly potentiate the antitumor activity of conventional chemotherapeutic drugs.
A Multiscale Approach for Whole-Slide Image Segmentation of five Tissue Classes in Urothelial Carcinoma Slides (2020)

In pathology labs worldwide, we see an increasing number of tissue samples that need to be assessed without the same increase in the number of pathologists. Computational pathology, where digital scans of histological samples called whole-slide images (WSI) are processed by computational tools, can be of help for the pathologists and is gaining research interests. Most research effort has been given to classify slides as being cancerous or not, localization of cancerous regions, and to the “big-four” in cancer: breast, lung, prostate, and bowel. Urothelial carcinoma, the most common form of bladder cancer, is expensive to follow up due to a high risk of recurrence, and grading systems have a high degree of inter- and intra-observer variability. The tissue samples of urothelial carcinoma contain a mixture of damaged tissue, blood, stroma, muscle, and urothelium, where it is mainly muscle and urothelium that is diagnostically relevant. A coarse segmentation of these tissue types would be useful to i) guide pathologists to the diagnostic relevant areas of the WSI, and ii) use as input in a computer-aided diagnostic (CAD) system. However, little work has been done on segmenting tissue types in WSIs, and on computational pathology for urothelial carcinoma in particular. In this work, we are using convolutional neural networks (CNN) for multiscale tile-wise classification and coarse segmentation, including both context and detail, by using three magnification levels: 25x, 100x, and 400x. 28 models were trained on weakly labeled data from 32 WSIs, where the best model got an F1-score of 96.5% across six classes. The multiscale models were consistently better than the single-scale models, demonstrating the benefit of combining multiple scales. No tissue-class ground-truth for complete WSIs exist, but the best models were used to segment seven unseen WSIs where the results were manually inspected by a pathologist and are considered as very promising.
Accurate Single-Nucleotide Polymorphism Allele Assignment in Trisomic or Duplicated Regions by Using a Single Base–Extension Assay with MALDI-TOF Mass Spectrometry (2011)

This approach enabled reliable genotyping of heterozygous trisomic samples and the determination of the origin of nondisjunction in Down syndrome family trios.
Identification of Human Immunodeficiency Virus Type 1 Subtype C Gag-, Tat-, Rev-, and Nef-Specific Elispot-Based Cytotoxic T-Lymphocyte Responses for AIDS Vaccine Design (2001)

The most severe human immunodeficiency virus type 1 (HIV-1) epidemic is occurring in southern Africa. It is caused by HIV-1 subtype C (HIV-1C). In this study we present the identification and analysis of cumulative cytotoxic T-lymphocyte (CTL) responses in the southern African country of Botswana. CTLs were shown to be an important component of the immune response to control HIV-1 infection. The definition of optimal and dominant epitopes across the HIV-1C genome that are targeted by CTL is critical for vaccine design. The characteristics of the predominant virus that causes the HIV-1 epidemic in a certain geographic area and also the genetic background of the population, through the distribution of common HLA class I alleles, might impact dominant CTL responses in the vaccinee and in the general population. The enzyme-linked immunospot (Elispot) gamma interferon assay has recently been shown to be a reliable tool to map optimal CTL epitopes, correlating well with other methods, such as intracellular staining, tetramer staining, and the classical chromium release assay. Using Elispot with overlapping synthetic peptides across Gag, Tat, Rev, and Nef, we analyzed HIV-1C-specific CTL responses of HIV-1-infected blood donors. Profiles of cumulative Elispot-based CTL responses combined with diversity and sequence consensus data provide an additional characterization of immunodominant regions across the HIV-1C genome. Results of the study suggest that the construction of a poly-epitope subtype-specific HIV-1 vaccine that includes multiple copies of immunodominant CTL epitopes across the viral genome, derived from predominant HIV-1 viruses, might be a logical approach to the design of a vaccine against AIDS.
An in situ measurement of intergranular coupling in magnetic film media (1993)

We describe an in situ nondestructive method to measure the intergranular coupling in magnetic thin film recording media based on Stoner–Wohlfarth switching theory [Philos. Trans. Roy. Soc. London A 240, 599 (1948)]. The method uses recording write and read heads and a disk test stand to measure a medium’s remanence curves from saturation and demagnetization. Using this technique, we have measured Henkel plots [Phys. Status. Solidi 7, 919 (1964)] for single layer and multiple layer longitudinal media, as well as a Henkel plot for a perpendicular thin film with a highly permeable underlayer, which cannot be obtained by the conventional vibrating sample magnetometer method.
The Mechanism of Mitochondrial Folate Transport by the Mitochondrial Folate Transporter (2010)

The mitochondrial folate transport protein (MFT) functions to transport folates into the mitochondrial matrix. The MFT is a member of a mitochondrial carrier family (MCF) of proteins that have a high degree of sequence and structural similarities, yet they transport vastly different substrates at high specificities. In this dissertation research, the folate-specific transport mechanism of the MFT was explored using experimental and computational techniques. MFT residues that differed from MCF consensus residues in conserved PxD/ExxK/R motifs and at a predicted substrate-binding site common to all MCF proteins were investigated. Site-directed mutagenesis of these anomalous residues in the MFT revealed that these residues were adapted for optimal folate transport, and that the MCF consensus residues at these positions were incompatible with folate transport. The structure of the MFT was predicted by homology modeling using the solved crystallographic structure of the ADP/ATP carrier as a template and this model was subjected to ~75 ns of molecular dynamics simulations. These simulations predicted a stepwise descent for the folate substrate into the MFT transport cavity and implicated several aromatic and basic residues in folate recognition and orientation. A predicted set of interactions at the base of the transport cavity between the MCF PxD/ExxK/R conserved motif residues did not appear static as previously hypothesized; these interactions appeared to be induced in the presence of the folate substrate. Therefore, we believe it is unlikely that these interactions form a barrier at the base of the transport cavity. We also investigated the role of the MFT in the compartmentalization of folate metabolism. Cell lines were created that could be induced with doxycycline to express either the cytosolic or mitochondrial isoform of the enzyme folylpoly-γ-glutamate synthetase (FPGS). The constructed cell lines were used to study the flux of folylpolyglutamates across the mitochondrial membrane. It appeared that cellular folylpolyglutamates are not transported across the mitochondrial membrane in either direction. We also demonstrated that many antifolates, including methotrexate and pemetrexed, impaired mitochondrial folate uptake. We believe that these folate analogs competitively inhibit the MFT and have purified the MFT protein for future analysis in reconstituted transport systems.
The single-stranded DNA-binding protein of Escherichia coli. (1990)

The single-stranded DNA-binding protein (SSB) of Escherichia coli is involved in all aspects of DNA metabolism: replication, repair, and recombination. In solution, the protein exists as a homotetramer of 18,843-kilodalton subunits. As it binds tightly and cooperatively to single-stranded DNA, it has become a prototypic model protein for studying protein-nucleic acid interactions. The sequences of the gene and protein are known, and the functional domains of subunit interaction, DNA binding, and protein-protein interactions have been probed by structure-function analyses of various mutations. The ssb gene has three promoters, one of which is inducible because it lies only two nucleotides from the LexA-binding site of the adjacent uvrA gene. Induction of the SOS response, however, does not lead to significant increases in SSB levels. The binding protein has several functions in DNA replication, including enhancement of helix destabilization by DNA helicases, prevention of reannealing of the single strands and protection from nuclease digestion, organization and stabilization of replication origins, primosome assembly, priming specificity, enhancement of replication fidelity, enhancement of polymerase processivity, and promotion of polymerase binding to the template. E. coli SSB is required for methyl-directed mismatch repair, induction of the SOS response, and recombinational repair. During recombination, SSB interacts with the RecBCD enzyme to find Chi sites, promotes binding of RecA protein, and promotes strand uptake.
A power controlled multiple access protocol for wireless packet networks (2002)

Multiple access-based collision avoidance MAC protocols have typically used fixed transmission power, and have not considered power control mechanisms based on the distance of the transmitter and receiver in order to improve spatial channel reuse. This work proposes PCMA, a power controlled multiple access wireless MAC protocol within the collision avoidance framework. PCMA generalizes the transmit-or-defer "on/off" collision avoidance model of current protocols to a more flexible "variable bounded power" collision suppression model. The algorithm is provisioned for ad hoc networks and does not require the presence of base stations to manage transmission power (i.e. it is decentralized). The advantage of implementing a power controlled protocol in an ad-hoc network is that source-destination pairs can be more tightly packed into the network allowing a greater number of simultaneous transmissions (spectral reuse). Our initial simulation results show that the PCMA can improve the throughput performance of the non-power controlled IEEE 802.11 by a factor of 2 with potential for additional scalability as source-destination pairs become more localized, thus providing a compelling reason for migrating to a new power controlled multiple access wireless MAC protocol standard.
A kinetic analysis of hybridoma growth and metabolism in batch and continuous suspension culture: Effect of nutrient concentration, dilution rate, and pH (1988)

Hybridomas are finding increased use for the production of a wide variety of monoclonal antibodies. Understanding the roles of physiological and environmental factors on the growth and metabolism of mammalian cells is a prerequisite for the development of rational scale-up procedures. An SP2/0-derived mouse hybridoma has been employed in the present work as a model system for hybridoma suspension culture. In preliminary shake flask studies to determine the effect of glucose and glutamine, it was found that the specific growth rate, the glucose and glutamine metabolic quotients, and the cumulative specific antibody production rate were independent of glucose concentration over the range commonly employed in cell cultures. Only the specific rate of glutamine uptake was found to depend on glutamine concentration. The cells were grown in continuous culture at constant pH and oxygen concentration at a variety of dilution rates. Specific substrate consumption rates and product formation rates were determined from the steady state concentrations. The specific glucose uptake rate deviated from the maintenance energy model(1) at low specific growth rates, probably due to changes in the metabolic pathways of the cells. Antibody production was not growth-associated; and higher specific antibody production rates were obtained at lower specific growth rates. The effect of pH on the metabolic quotients was also determined. An optimum in viable cell concentration was obtained between pH 7.1 and 7.4. The viable cell number and viability decreased dramatically at pH 6.8. At pH 7.7 the viable cell concentration initially decreased, but then recovered to values typical of pH 7.1-7.4. Higher specific nutrient consumption rates were found at the extreme pH values; however, glucose consumption was inhibited at low pH. The pH history also influenced the behavior at a given pH. Higher antibody metabolic quotients were obtained at the extreme pH values. Together with the effect of specific growth rate, this suggests higher antibody production under environmental or nutritional stress.
Amorphous silicon active pixel sensor readout circuit for digital imaging (2003)

The most widely used architecture in large-area amorphous silicon (a-Si) flat panel imagers is a passive pixel sensor (PPS), which consists of a detector and a readout switch. While the PPS has the advantage of being compact and amenable toward high-resolution imaging, reading small PPS output signals requires external column charge amplifiers that produce additional noise and reduce the minimum readable sensor input signal. This work presents a current-mediated amorphous silicon active pixel readout circuit that performs on-pixel amplification of noise-vulnerable sensor input signals to minimize the effect of external readout noise sources associated with "off-chip" charge amplifiers. Results indicate excellent small-signal linearity along with a high, and programmable, charge gain. In addition, the active pixel circuit shows immunity to shift in threshold voltage that is characteristic of a-Si devices. Preliminary circuit noise results and analysis appear promising for its use in noise-sensitive, large-area, medical diagnostic imaging applications such as digital fluoroscopy.
Surface topography change induced by poling in Ge doped silica glass films. (2003)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text B. Poumellec, Y. Ren, and M. Kristensen, "Surface topography change induced by poling in Ge doped silica glass films.," in Bragg Gratings, Photosensitivity, and Poling in Glass Waveguides, Technical Digest (Optica Publishing Group, 2003), paper MD38. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Prognostic significance of DNA cytometry in cutaneous malignant lymphomas (1991)

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML.