gebhart/patrepeval huggingface dataset:
Coagulopathic complications in breast cancer (2003)

Patients with cancer are highly susceptible to thromboembolic complications, which account for a significant percentage of the morbidity and mortality of the disease. Up to 15% of patients with clinically overt cancer present with venous thromboembolism during the course of their disease. Moreover, patients with cancer represent 20% of all patients in whom deep venous thrombosis and pulmonary embolism are diagnosed. This prothrombotic state in cancer can occur due to the ability of tumor cells to directly activate the blood-clotting cascade and cause thrombosis or induce procoagulant properties and inhibit anticoagulant properties of vascular endothelial cells, platelets, monocytes, and macrophages. It also is well established that this prothrombotic tendency in patients with cancer can be enhanced greatly by anticancer treatments, such as surgery and chemotherapy. This phenomenon can be seen in patients with breast cancer, particularly after surgery and chemotherapy. Increased clotting risk also is associated with the use of central venous access devices, commonly used to administer chemotherapeutic agents in patients with cancer. Thrombosis prophylaxis, therefore, should be considered for patients with breast cancer who are at risk before and during intervention. In the current review, the authors discuss the problem of thromboembolism in patients with breast cancer who are undergoing therapy, the mechanisms by which thromboembolisms occur, and the potential strategies by which these events may be prevented. Better understanding of these pathogenetic pathways may lead to the development of more targeted strategies to prevent thromboembolism in patients with cancer.
Focal plane array spectrometer: miniaturization effort for space optical instruments (2011)

A concept of a compact imaging spectrometer component based on an integrated waveguide array is elaborated and its design rules presented. The component, a focal plane array spectrometer (FPAS), is used in a similar way as a CMOS detector array or a CCD in a camera. The classical spectrometer, for instance an optical grating spectrometer, disappears from the optical system. The whole instrument is therefore reduced to the imaging optics and the FPAS in the focal plane which takes over the function of the spectrometer and detector array. Its potential for very high spectral resolution, minimal size, simple instrument integration, modularity and ruggedness makes it interesting for commercial and special applications like space. Two typical space optical instruments are reconceived using the FPAS with the result of a potential volume reduction of a factor five to eight while keeping the same performances. Also the specifications of simple and generic spectrometers based on the proposed component concept are very promising with respect to spectral resolution, volume and simplicity of instrument design and manufacturing.
6-Aza-2-thiothymine: a matrix for MALDI spectra of oligonucleotides (1995)

Journal Article 6-Aza-2-thiothymine: a matrix for MALDI spectra of oligonucleotides Get access Paolo Lecchi, Paolo Lecchi * Laboratory of Analytical Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesda, MD 20892-0805, USA * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Han M. T. Le, Han M. T. Le Laboratory of Analytical Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesda, MD 20892-0805, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Lewis K. Pannell Lewis K. Pannell Laboratory of Analytical Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of HealthBethesda, MD 20892-0805, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 23, Issue 7, 11 April 1995, Pages 1276–1277, https://doi.org/10.1093/nar/23.7.1276 Published: 11 April 1995 Article history Received: 03 January 1995 Revision received: 23 February 1995 Accepted: 23 February 1995 Published: 11 April 1995
Green chemistry: The development of cross-dehydrogenative coupling (CDC) for chemical synthesis (2006)

Abstract Social, economic, and environmental concerns about chemical production have been increasing. These concerns all originate from the inefficiency of conventional chemical syntheses. On the basis of the "E-factor", a concept of the "extended E-factor" is proposed in the article and is used to correlate various industrial sectors and the average number of synthetic steps involved in those sectors. Based on this analysis, the most fundamental way to eliminate waste formation is to develop new chemical reactivity that can greatly shorten the steps involved in a chemical synthesis. In classical organic transformations, a "functional group" is required. In efforts to develop new chemical reactivities that do not need extra steps for generating functional groups, we have recently developed various cross-dehydrogenative coupling (CDC) methodologies to construct functional molecules by directly using C-H bonds. This article describes the progress of our group's research endeavor.
CD40-activated surface IgD-positive lymphocytes constitute the long term IL-4-dependent proliferating B cell pool. (1994)

In vitro, B cells undergo long term proliferation when triggered through their CD40 surface molecule and in the presence of IL-4. Here, we show that cells that proliferate in this culture system lose their germinal center (GC) features and acquire or maintain non-GC markers. When separated by the magnetic cell separation system, both sIgD+ and sIgD- B cells can proliferate in this culture system, sIgD+ B cells exhibiting a higher rate of growth than sIgD- cells. Simultaneous flow cytometric measurement of sIgD and DNA content revealed that B lymphocytes can keep their sIgD after entry into cell cycle. Experiments using G8 Id-positive B lymphocytes allowed us to follow the evolution of sIgD+ and sIgD- cells in a reconstituted B cell population. Long term proliferating cells are sIgD+/sIgM(+)-derived B lymphocytes whereas the initial sIgD-/sIgM- cells are lost. Taken together, these data show that anti-CD40 + IL-4 activated sIgD+ B blasts express non-GC characteristics and that sIgD+ B cells preferentially proliferate in the CD40 system. The possible in vivo role of IL-4 + CD40 signaling is discussed.
Cooperative DNA binding of the human HoxB5 (Hox-2.1) protein is under redox regulation in vitro. (1993)

The human HoxB5 (Hox-2.1) gene product is a sequence-specific DNA binding protein. Cooperative interactions stabilize in vitro DNA binding of the HoxB5 protein to tandem binding sites by at least 100-fold relative to binding to a single site. The HoxB5 homeodomain is sufficient for sequence-specific DNA binding but not for cooperative DNA binding. Here we report that the additional protein sequence required for cooperativity is a small domain adjacent to the homeodomain on the amino-terminal side. We further show that cooperative DNA binding is under redox regulation. The HoxB5 protein binds to DNA in vitro both when oxidized or reduced but binds cooperatively only when oxidized. Mutational analysis has revealed that the cysteine residue in the turn between homeodomain helices 2 and 3 is necessary for cooperative binding and redox regulation. The enhanced DNA binding of oxidized HoxB5 protein is the opposite of the redox regulation reported for other mammalian transcription factors such as Fos, Jun, USF, NF-kappa B, c-Myb, and v-Rel, in which oxidation of cysteine residues inhibits DNA binding. Thus, specific oxidation of nuclear proteins is a potential regulatory mechanism that can act to either decrease or increase their DNA binding activity.
Purification and characterization of an immunoglobulin A1 protease from Bacteroides melaninogenicus (1984)

Attention has recently been focused on bacterial proteases with the capacity to cleave immunoglobulin A (IgA proteases) as possible pathogenic factors in bacterial meningitis, gonorrhoea, and destructive periodontal disease. Here, we describe a method for the rapid purification of a specific IgA1 protease from Bacteroides melaninogenicus. The IgA1 protease was purified 6,172-fold with a yield of 9% by ammonium sulfate precipitation, DEAE-ion exchange chromatography, and separation on a preparative TSK-G 3000SWG high-pressure gel permeation chromatography column. The enzyme was specific for human IgA1 and cleaved a prolyl-seryl peptide bond in the hinge region of the alpha 1 chain between residues 223 and 224. The molecular weight of the enzyme was 62,000, the isoelectric point was 5.0, and the Km was 3.4 X 10(-6). The enzyme was active over a broad pH range and had maximal activity at pH 5.0. B. melaninogenicus IgA1 protease was classified as a thiol protease on the basis of its inhibition by traditional protease inhibitors and the fact that it was active only under reducing conditions.
Effective Control of Recalcitrant Pruritus by Bevacizumab: A Possible Role for Vascular Endothelial Growth Factor in Chronic Itch? (2013)

Prurigo is a difficult to treat condition characterized by severe pruritus presenting with chronic secondary scratch lesions. We report here a dramatic improvement in pruritus in a patient with prurigo simplex who was being treated with bevacizumab, a monoclonal vascular endothelial growth factor (VEGF) antibody. On the basis of the increased VEGF expression measured in the skin of this patient, serum levels of VEGF were subsequently analysed in 27 consecutive patients with prurigo and 19 healthy controls. VEGF levels were significantly increased in the serum of patients with prurigo. Moreover, VEGF concentrations correlated with physician-assessed disease activity. Based on these observations, we speculate that VEGF is involved in the pathophysiology of prurigo.
Identification of class-determining residues in G protein-coupled receptors by sequence analysis. (1997)

G protein-coupled receptors (GPCRs) form a large superfamily of receptors that are characterised by a seven transmembrane helical motif. The functions they perform, such as binding ligands and G proteins, are related to the presence of certain amino acids in critical positions. We have developed a computational sequence pattern correlation technique for the recognition of such function-determining residues. The method searches for residues that are conserved in one class of proteins with a certain function but are different in other classes. The basic idea is that such residues are probably involved in this particular function. This technique was used to find residues that play a role in the binding of endogenous as well as exogenous ligands to various receptors. Many of the residues that were detected have been experimentally determined as important for ligand binding. More importantly, however, we also detected residues that are interesting targets for future mutation studies aimed at elucidating the sequence-function relationship in GPCRs. The information obtained may help improve three-dimensional GPCR models and can be useful for the study of receptor-ligand interactions.
Substrate specificity of the lipase fromCandida parapsilosis (1995)

Substrate specificity of the acyltransferase activity of the lipase (EC 3.1.1.3) from Candida parapsilosis CBS 604 was studied in aqueous media. The specificity toward both acid and alcohol parts of a large number of acylglycerols and aliphatic esters was investigated. This lipase showed a high activity in the presence of esters with long-chain fatty acids and particularly unsaturated fatty acids with a cis-delta 9 double bond. It was observed that the activity profile depended not only on the alcohol part of the acyl ester, but also on the temperature of the reactant medium. The best lipid substrates had their melting point between -40 to +20 degrees C, 14 to 18 carbon atoms in the acyl group and 1 to 4 carbon atoms in the alkyl group. The enzyme, defined as an acyltransferase in a previous paper, showed a high affinity for primary and secondary alcohols with a short carbon chain (1 to 5 carbon atoms) as acyl acceptors. The influence of free alcohols in the reactant medium on the hydrolysis and alcoholysis activities of the enzyme is discussed. Two phenomena seem to be involved, depending on the alcohol: competition with water for the acyltransfer reaction and lipid substrate dilution when the alcohol places at the oil/water interface.
Feature Selection Using a Multilayer Perceptron (1990)

The problem of selecting the best set of features for target recognition using a multilayer perceptron is addressed in this paper. A technique has been developed which analyzes the weights in a multilayer perceptron to determine which features the network finds important and which are unimportant. A brief introduction to the use of multilayer perceptrons for classification and the training rules available is followed by the mathematical development of the saliency measure for multilayer perceptrons. The technique is applied to two different image databases and is found to be consistent with statistical techniques and independent of the network initial conditions. The saliency measure is then used to compare the results of two different training rules on a target recognition problem. 1 Introduction Recently there has been a great deal of interest in the use of multilayer perceptrons as classifiers in pattern recognition problems (see, for example, [11]). Unfortunately, little ...
Preparation and Thermodynamic Stability of Micron-Sized, Monodisperse Composite Polymer Particles of Disc-like Shapes by Seeded Dispersion Polymerization (2007)

Micron-sized, monodisperse composite polymer particles having "disc-like" and "polyhedral" shapes were prepared by seeded dispersion polymerization of 2-ethylhexylmethacrylate (EHMA) with 2.67-mum-sized polystyrene (PS) seed particles in methanol/water media in the presence of droplets of various saturated hydrocarbons and evaporation of the hydrocarbon after the polymerization. Such nonspherical shapes were based on the volume reduction due to the evaporation. The primary factors influencing the particle shape seemed to be the absorption rate of the hydrocarbon into the resulting PS/poly(EHMA)/hydrocarbon composite particles during the polymerization, which affected the viscosities and the volumes of the PS and poly(EHMA) phases. It was found that the morphological development during the polymerization was retarded at "hamburger-like" morphology, which is a precursor of the disc-like particle, although this morphology is a thermodynamically metastable state.
A functional GTP-binding motif is necessary for antiviral activity of Mx proteins (1993)

Mx proteins are interferon-induced GTPases that inhibit the multiplication of certain negative-stranded RNA viruses. However, it has been unclear whether GTPase activity is necessary for antiviral function. Here, we have introduced mutations into the tripartite GTP-binding consensus elements of the human MxA and mouse Mx1 proteins. The invariant lysine residue of the first consensus motif, which interacts with the beta- and gamma-phosphates of bound GTP in other GTPases, was deleted or replaced by methionine or alanine. These Mx mutants and appropriate controls were then tested for antiviral activity, GTP-binding capacity, and GTPase activity. We found a direct correlation between the GTP-binding capacities and GTP hydrolysis activities of the purified Mx mutants in vitro and their antiviral activities in transfected 3T3 cells, demonstrating that a functional GTP-binding motif is necessary for virus inhibition. Our results, thus, firmly establish antiviral activity as a novel function of a GTPase, emphasizing the enormous functional diversity of GTPase superfamily members.
The Impact of Consumer Characteristics on Preferences for Selected Apple Varieties (1997)

This study examines consumer varietal preferences for three apple varieties. Paired sensory and visual tests were conducted on college age individuals age 25 and under with New England grown McIntosh and Empire apples and Washington State grown Red Delicious. Qualitative choice models were used in the study to assess the impact of consumer characteristics on their choice of most preferred apple variety from the sensory and visual tests. In the blind-sensory tests, consumers demonstrate their ability to identify the sensory attributes of their most preferred apple variety, a dominant factor affecting their choices of apples. On the other hand, visual test results indicate that consumer preference for apple varieties differs by age and sex of the consumer.
Adeno-Associated Viral Vectors Based on Serotype 3b Use Components of the Fibroblast Growth Factor Receptor Signaling Complex for Efficient Transduction (2021)

Adeno-associated virus type 3b (AAV3b) has been largely ignored by gene therapists because of the inability of vectors based on this serotype to transduce target tissues efficiently. Here we describe a phenomenon unique to AAV3b in that vectors based on this serotype mediate enhanced transduction in the presence of heparin. Among the many biological functions attributed to heparin, its interaction with, and ability to regulate, several growth factors (GFs) and growth factor receptors (GFRs) has been well characterized. Using GFR-overexpressing cell lines, soluble GFs and heparins, as well as specific GFR inhibitors, we have demonstrated a requirement for fibroblast growth factor receptor-2 (FGFR2) and FGF1 in the heparin-mediated augmentation of AAV3b vector transduction. In contrast to AAV2, we establish that heparin can be used as an adjunct with AAV3b to further increase transduction in a variety of cells and target tissues, additionally suggesting that AAV3b may be an attractive viral vector for clinical use during procedures in which heparin is used. In summary, AAV3b exhibits FGFR2-dependent, markedly enhanced transduction efficiency in the presence of heparin and FGFs, which could make it a useful vector for gene therapy in a variety of human diseases.
Role of NtcB in Activation of Nitrate Assimilation Genes in the Cyanobacterium Synechocystis sp. Strain PCC 6803 (2001)

In Synechocystis sp. strain PCC 6803, the genes encoding the proteins involved in nitrate assimilation are organized into two transcription units, nrtABCD-narB and nirA, the expression of which was repressed by ammonium and induced by inhibition of ammonium assimilation, suggesting involvement of NtcA in the transcriptional regulation. Under inducing conditions, expression of the two transcription units was enhanced by nitrite, suggesting regulation by NtcB, the nitrite-responsive transcriptional enhancer we previously identified in Synechococcus sp. strain PCC 7942. The slr0395 gene, which encodes a protein 47% identical to Synechococcus NtcB, was identified as the Synechocystis ntcB gene, on the basis of the inability of an slr0395 mutant to rapidly accumulate the transcripts of the nitrate assimilation genes upon induction and to respond to nitrite. While Synechococcus NtcB strictly requires nitrite for its action, Synechocystis NtcB enhanced transcription significantly even in the absence of nitrite. Whereas the Synechococcus ntcB mutant expresses the nitrate assimilation genes to a significant level in an NtcA-dependent manner, the Synechocystis ntcB mutant showed only low-level expression of the nitrate assimilation genes, indicating that NtcA by itself cannot efficiently promote expression of these genes in Synechocystis. Activities of the nitrate assimilation enzymes in the Synechocystis ntcB mutant were consequently low, being 40 to 50% of the wild-type level, and the cells grew on nitrate at a rate approximately threefold lower than that of the wild-type strain. These results showed that the contribution of NtcB to the expression of nitrate assimilation capability varies considerably among different strains of cyanobacteria.
CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles (2018)

Harnessing CRISPR-Cas9 technology provides an unprecedented ability to modify genomic loci via DNA double-strand break (DSB) induction and repair. We analyzed nonhomologous end-joining (NHEJ) repair induced by Cas9 in budding yeast and found that the orientation of binding of Cas9 and its guide RNA (gRNA) profoundly influences the pattern of insertion/deletions (indels) at the site of cleavage. A common indel created by Cas9 is a 1-bp (+1) insertion that appears to result from Cas9 creating a 1-nt 5' overhang that is filled in by a DNA polymerase and ligated. The origin of +1 insertions was investigated by using two gRNAs with PAM sequences located on opposite DNA strands but designed to cleave the same sequence. These templated +1 insertions are dependent on the X-family DNA polymerase, Pol4. Deleting Pol4 also eliminated +2 and +3 insertions, which are biased toward homonucleotide insertions. Using inverted PAM sequences, we also found significant differences in overall NHEJ efficiency and repair profiles, suggesting that the binding of the Cas9:gRNA complex influences subsequent NHEJ processing. As with events induced by the site-specific HO endonuclease, CRISPR-Cas9-mediated NHEJ repair depends on the Ku heterodimer and DNA ligase 4. Cas9 events are highly dependent on the Mre11-Rad50-Xrs2 complex, independent of Mre11's nuclease activity. Inspection of the outcomes of a large number of Cas9 cleavage events in mammalian cells reveals a similar templated origin of +1 insertions in human cells, but also a significant frequency of similarly templated +2 insertions.
Evolutionary relationships among Magnetospirillum strains inferred from phylogenetic analysis of 16S rDNA sequences (1993)

We have investigated the evolutionary relationships between two facultatively anaerobic Magnetospirillum strains (AMB-1 and MGT-1) and fastidious, obligately microaerophilic species, such as Magnetospirillum magnetotacticum, using a molecular phylogenetic approach. Genomic DNA from strains MGT-1 and AMB-1 was used as a template for amplification of the genes coding for 16S rRNA (16S rDNA) by the polymerase chain reaction. Amplified DNA fragments were sequenced (1,424 bp) and compared with sequences for M. magnetotacticum MS-1 and Magnetospirillum gryphiswaldense MSR-1. Phylogenetic analysis of the aligned 16S rDNA sequences indicated that the two new magnetic spirilla, AMB-1 and MGT-1, lie within the alpha subdivision (alpha-1) of the eubacterial group Proteobacteria and are closely related to Rhodospirillum fulvum and to several endosymbiotic bacteria. Strains AMB-1, MGT-1, and MS-1 formed a cluster, termed group I, in which they were more closely related to each other than to group II, which contained M. gryphiswaldense MSR-1. Group I strains were also physiologically distinct from strain MSR-1. Sequence alignment studies allowed elucidation of genus-specific regions of the 16S rDNA, and oligonucleotide primers complementary to two of these regions were used to develop a specific polymerase chain reaction assay for detection of magnetic spirilla in natural samples.