gebhart/patrepeval huggingface dataset:
Drug Delivery via the Respiratory Tract (1994)

Inhalation offers an enormous absorptive surface area for rapid drug absorption and substantial absorption of polypeptides. Due to slow clearance from the lower lung, even compounds with very small absorption rates can be absorbed in significant quantities over 10-12h periods. Aerosol dosimetry problems can also be minimized when lung-normal patients are considered. In the near future, optimal formulations will be combined with modified aerosol delivery devices to achieve reproducible dosing. These will be used as alternatives to parenteral delivery for drug doses of the order of milligrams or less. Research on the molecular structural dependence of lung disposition is in its infancy. Absorption kinetics for small molecules are known to depend on lipophilicity and molecular size. For macromolecules however, electronic charge and site of deposition may be additional determinants of bioavailability. Carrier-mediated absorption processes may also be important. The pulmonary absorption of a number of molecules is reviewed with special emphasis on new and promising products of biotechnology like human insulin and human growth hormone. Delivery improvements in the future should ensure, ideally, that nondenatured, monomeric pure compounds are delivered reproducibly and predominantly to the lung itself, so that these compounds may elicit reproducible systemic effects following absorption.
Strongly Directed Emission from Controlled-Spontaneous-Emission Electroluminescent Diodes with Europium Complex as an Emitter (1994)

Multilayer electroluminescent diodes with sharp red emission were fabricated using a new europium complex as an emitter. Microcavity structures were introduced into the EL diodes with sharp red emission. The device structure consisted of a dielectric reflector composed of SiO 2 /TiO 2 bilayers, an indium-tin-oxide electrode, a hole transport layer, a europium complex as an emission layer, an electron transport layer and a MgAg electrode. The dielectric reflector and the MgAg metal electrode constituted a planer microcavity, and sharply directed emission from the europium complex was observed when operated under dc drive voltage. The relationship between emission angle and the size of the microcavity was discussed.
Correction: Efficient in situ N-heterocyclic carbene palladium(ii) generated from Pd(OAc)2 catalysts for carbonylative Suzuki coupling reactions of arylboronic acids with 2-bromopyridine under inert conditions leading to unsymmetrical arylpyridine ketones: synthesis, characterization and cytotoxic activities (2018)

[This corrects the article DOI: 10.1039/C8RA08897G.].
HIV-Protease Inhibitors (1998)

Inhibitors of human immunodeficiency virus (HIV)–encoded protease, combined with nucleoside analogues with antiretroviral activity, cause profound and sustained suppression of viral replication, reduce morbidity, and prolong life in patients with HIV infection.13 Recent guidelines recommend that initial treatment of all HIV-infected patients include the administration of an HIV-protease inhibitor.4 The HIV-Encoded ProteaseThe HIV protease, encoded in the 5' end of the pol gene, is expressed as part of the gag–pol polyprotein (Figure 1A, Figure 1B, and Figure 1C). This gene encodes a 99-amino-acid protein. Homodimers of this protein have the aspartyl protease activity that is typical of retroviral proteases; monomers . . .
Multiple Surface Plasmon Modes for a Colloidal Solution of Nanoporous Gold Nanorods and Their Comparison to Smooth Gold Nanorods (2008)

The paper represents a novel approach to investigating localized surface plasmon (LSP) resonance modes of nanoporous Au nanorods (NRs) in a solution phase with control over surface morphology. Au NRs, which have distinctive features such as nanopores and ligaments, showed interesting LSP resonance modes depending on the surface morphology and the total length of the structure. Compared with the analogous smooth surface NRs, the LSP modes of nanoporous NRs are red-shifted, which can be interpreted as a longer effective rod length and larger amplitude of plasmon oscillation.
Anti-CD20 Chimeric Monoclonal Antibody Treatment of Refractory Immune-Mediated Thrombocytopenia in a Patient with Chronic Graft-versus-Host Disease (2000)

The efficacy of rituximab for the treatment of immune-mediated thrombocytopenia suggests that this drug may have activity in other autoimmune diseases or chronic graft-versus-host disease.
The neutrophil as a cellular source of chemokines (2000)

Neutrophils are known to play an important role in inflammatory responses by virtue of their ability to perform a series of effector functions that collectively represent a major mechanism of innate immunity against injury and infection. In recent years, however, it has become obvious that the contribution of neutrophils to host defence and natural immunity extends well beyond their traditional role as professional phagocytes. Indeed, neutrophils can be induced to express a number of genes whose products lie at the core of inflammatory and immune responses. These include not only Fc receptors, complement components, cationic antimicrobial and NADPH oxidase proteins, but also a variety of cytokines (including tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-1R alpha, IL-12 and vascular endothelial growth factor), and chemokines such as IL-8, growth-related gene product, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, interferon-gamma-inducible protein of 10 kDa and monokine induced by interferon-gamma. Because these chemokines are primarily chemotactic for neutrophils, monocytes, immature dendritic cells and T-lymphocyte subsets, a potential role for neutrophils in orchestrating the sequential recruitment of distinct leukocyte types to the inflamed tissue is likely to occur. The purpose of this review is to summarize the essential features of the production of chemokines by polymorphonuclear neutrophil leukocytes and the contribution that we have made to characterize some aspects of this newly discovered crucial function of neutrophils.
Glutamate and the pathophysiology of hypoxic–ischemic brain damage (1986)

Information obtained over the past 25 years indicates that the amino acid glutamate functions as a fast excitatory transmitter in the mammalian brain. Studies completed during the last 15 years have also demonstrated that glutamate is a powerful neurotoxin, capable of killing neurons in the central nervous system when its extracellular concentration is sufficiently high. Recent experiments in a variety of preparations have shown that either blockade of synaptic transmission or the specific antagonism of postsynaptic glutamate receptors greatly diminishes the sensitivity of central neurons to hypoxia and ischemia. These experiments suggest that glutamate plays a key role in ischemic brain damage, and that drugs which decrease the accumulation of glutamate or block its postsynaptic effects may be a rational therapy for stroke.
Novel Small Molecule Bradykinin B 2 Receptor Antagonists (2009)

Blockade of the bradykinin B(2) receptor provides therapeutic benefit in hereditary angioedema (HAE) and potentially in many other diseases. Herein, we describe the development of highly potent B(2) receptor antagonists with a molecular weight of approximately 500 g/mol. First, known quinoline-based B(2) receptor antagonists were stripped down to their shared core motif 53, which turned out to be the minimum pharmacophore. Targeted modifications of 53 resulted in the highly water-soluble lead compound 8a. Extensive exploration of its structure-activity relationship resulted in a series of highly potent B(2) receptor antagonists, featuring a hydrogen bond accepting functionality, which presumably interacts with the side chain of Asn-107 of the B(2) receptor. Optimization of the microsomal stability and cytochrome P450 inhibition eventually led to the discovery of the highly potent and orally available B(2) receptor antagonist 52e (JSM10292), which showed the best overall properties.
cDNA and Gene Structure for a Human Subtilisin-Like Protease with Cleavage Specificity for Paired Basic Amino Acid Residues (1991)

A cDNA encoding the human fur gene product was isolated from a human hepatoma cell line. The cDNA encodes a protein with significant amino acid sequence identity to the prokaryotic subtilisin family of serine proteases. More extensive sequence identity was found when the protein was compared with eukaryotic proteases such as PRB1 of Saccharomyces cerevisiae, and with PC2 and PC3, the only other known mammalian subtilisin-like proteases. In contrast to these proteins, however, the fur gene product shares a more extensive topographic and functional homology with the KEX2 endoprotease of S. cerevisiae. Each protease contains a signal peptide, a glycosylated extra cytoplasmic domain, a hydrophobic membrane-spanning region, and a short, hydrophilic "tail" sequence. As with KEX2, the expressed human protease was shown to cleave mammalian proproteins at their paired basic amino acid processing sites. We have, therefore, proposed the function-based acronym PACE (paired basic amino acid cleaving enzyme) for this prototypic mammalian proprotein processing enzyme.
The complete amino acid sequence of antiviral protein from the seeds of pokeweed (Phytolacca americana). (1990)

The complete amino acid sequence of antiviral protein from the seeds of pokeweed (Phytolacca americana) has been determined. This has been done by the sequence analysis of peptides derived by enzymatic digestion with trypsin, pepsin, and lysylendopeptidase, as well as by chemical cleavage with cyanogen bromide. The protein consists of 261 amino acid residues containing two disulfide bonds and has a calculated molecular mass of 29167 Da. The two disulfide bonds connect Cys-34 to Cys-258 and Cys-84 to Cys-105. Comparison of this sequence with the sequence of the ricin A-chain shows that there are identical residues at 76 positions in the two molecules (30% identity), having an extended region of highly conserved sequence at positions 170-183 (IQMXSEAARFXYIE). In contrast, the internal regions at positions 77-119 and 141-169 and the C-terminal 15 amino acid residues are less homologous in the two proteins.
The Syntheses of the Crown Ethers Possessing 2,6-Pyridino Moieties. (1983)

In an attempt to synthesize "Type 2" nicotinic acid crown ethers with a 3-carbinol appendage group, unexpected facile etherification was encountered during the cleavage of the tetrahydropyranyl (THP) group in acidic alcoholic media. The rationale for this reaction was provided by the examination of reactions with non-cyclic model compounds, and their THP derivatives in order to isolate any effects of the crown ether bridge. The 2,6-disubstituted dialkoxy groups were found to contribute to the stabilization of the carbonium ion derived from the protonation of the 3-pyridyl carbinols. Thus, nicotinic crown ether with a 3-carbinol group was prepared with the exclusion of alcoholic media. The preparation of "Type 2" nicotinic acid crown ethers with an aldehyde group was attempted. 3-Formylpyridino crown ether was obtained directly from the reaction of disodium pentaethylene glycolate and the diethoxy acetal derivative of 2,6-dichloro-3-formylpyridine. The syntheses of crown ethers, such as 18-crown-6 and 21-crown-7, with tripyridino moieties were accomplished. The Boekelheide rearrangement was employed to functionalize terminal pyridyl methyl groups to give the corresponding diol, which served as an important intermediate in subsequent cyclization procedures. The 1:1-ketalic macrocycles were transformed to 1,5-diketonic macrocycles, which then were converted to the corresponding tripyridino crown ethers. The X-ray crystal structure of a tripyridino macrocycle trihydrate indicated that a new type of mu-H-bonding for pyridine and water. The same method utilized for tripyridine macrocycles was applied to the synthesis of a pentapyridine macrocycle with a single ether bridge. The ether linkage was formed at the early stage of synthesis. The middle ring of the pentapyridine moiety was formed from an appropriate 1,5-diketone precursour at the last stage of synthesis. In order to prepare a cyclic hexapyridine the bisformyldipyridine was converted to a 1,3-dithiane derivative, which was cyclized with 1,3-dibromopropane. The macrocyclic bis(1,3-dithiane) was cleaved to a tetraketone. And finally cyclic hexapyridine was prepared from the reaction of the tetraketonic macrocycle and hydroxylamine under acidic condition.
Serial siphon valving for centrifugal microfluidic platforms (2009)

Today, the focus in microfluidic platforms for diagnostics is on the integration of several analysis steps toward sample-to-answer systems. One of the main challenges to integration is the requirement for serial valving to allow the sequential release of fluids in a temporally and spatially controlled manner. The advantages offered by centrifugal microfluidic platforms make them excellent candidates for integration of biological analysis steps, yet they are limited by the lack of robust serial valving technologies. This is especially true for the majority of centrifugal microfluidic devices that rely on hydrophilic surfaces, where few passive serial valving techniques function reliably. Building on the useful functionality of centrifugal microfluidic siphoning previously shown, a novel serial siphon valve is introduced that relies on multiple, inline siphons to provide for a better controlled, sequential release of fluids. The introduction of this novel concept is followed by an analytical analysis of the device. Proof-of-concept is also demonstrated, and examples are provided to illustrate the range of functionality of the serial siphon valve. The serial siphon is shown to be robust and reproducible, with variability caused by the dependence on contact angle, rotation velocity, and fluidic properties (viz., surface tension) significantly reduced compared to current microfluidic, centrifugal serial valving technologies.
Escherichia coli aspartate transcarbamylase: a novel marker for studies of gene amplification and expression in mammalian cells. (1986)

Eucaryotic expression vectors containing the Escherichia coli pyrB gene (pyrB encodes the catalytic subunit of aspartate transcarbamylase [ATCase]) and the Tn5 phosphotransferase gene (G418 resistance module) were transfected into a mutant Chinese hamster ovary cell line possessing a CAD multifunctional protein lacking ATCase activity. G418-resistant transformants were isolated and analyzed for ATCase activity, the ability to complement the CAD ATCase defect, and the ability to resist high concentrations of the ATCase inhibitor N-(phosphonacetyl)-L-aspartate (PALA) by amplifying the donated pyrB gene sequences. We report that bacterial ATCase is expressed in these lines, that it complements the CAD ATCase defect in trans, and that its amplification engenders PALA resistance. In addition, we derived rapid and sensitive assay conditions which enable the determination of bacterial ATCase enzyme activity in the presence of mammalian ATCase.
Noninvasive estimation of tissue temperature response to heating fields using diagnostic ultrasound (1995)

A noninvasive technique for monitoring tissue temperature changes due to heating fields using diagnostic ultrasound is described in this paper. The approach is based on the discrete scattering model used in the tissue characterization literature and the observation that most biological tissues are semi-regular scattering lattices. It has been demonstrated by many researchers and verified by us that the spectrum of the backscattered radio frequency (RF) signal collected with a diagnostic ultrasound transducer from a semi-regular tissue sample exhibits harmonically related resonances at frequencies determined by the average spacing between scatterers along a segment of the A-line. It is shown theoretically and demonstrated experimentally (for phantom, in vitro, and in vivo media) that these resonances change with changes in the tissue temperature within the processing window. In fact, changes in the resonances (delta f) are linearly proportional to changes in the temperature (delta T), with the proportionality constant being determined by changes in the speed of sound with temperature and the linear coefficient of thermal expansion of the tissue. Autoregressive (AR) model-based methods aid in the estimation of delta f. It should be emphasized that this new technique is not a time of flight velocimetric one, so it represents a departure from previously used ultrasonic methods for tissue temperature estimation.
A Rapid, Fully Automated, Molecular-Based Assay Accurately Analyzes Sentinel Lymph Nodes for the Presence of Metastatic Breast Cancer (2006)

A rapid, fully automated QRT-PCR assay definitively characterizes breast cancer SLN with accuracy equal to conventional pathology. This approach is superior to intraoperative SLN analysis and can provide standardized, objective results to assist in pathologic diagnosis.
Masked Michael Acceptors in Poly(phenyleneethynylene)s for Facile Conjugation (2006)

Poly(phenyleneethynylene)s (PPEs) capable of reacting with thiol-containing molecules have been designed and synthesized with number-average molecular weights ranging from 8000 to 11 000. The PPEs contain pendent masked maleimide units available to participate in conjugate additions and Diels−Alder chemistries after being thermally activated. If the maleimide group is left unmasked during palladium-catalyzed cross-coupling polymerization, it leads to side reactions and the production only of short chain oligomers (Mn < 3000, DP ∼ 4). Reversible Diels−Alder reactions between the maleimides and furan were determined to be a very effective method to produce a masked Michael acceptor that can be unveiled after polymerization under relatively mild thermal conditions. Cycloreversion to the maleimide has been monitored by thermogravimetric analysis (TGA), TGA-MS, IR, and NMR. A PPE containing the masked maleimide unit has been modified with a thiolated carboxy-X-rhodamine (ROX) dye, and the resulting absorbance and fluorescence spectra as well as gel permeation chromatograms (GPC) are presented.
Detection of minimal residual disease in acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor delta chain sequences (1989)

Human T-cell receptor (TCR) delta-chain diversity mainly originates from high junctional variability, since only a limited number of germline elements is available. This extraordinary diversity at the V.J junction, due to the use of two D delta elements and extensive incorporation of N nucleotides, constitutes a specific clonal marker for cell populations exhibiting rearranged TCR delta genes. To this end we amplified in vitro by polymerase chain reaction (PCR) the TCR delta junctional region of five acute lymphoblastic leukemias (ALL), isolated respective DNA fragments, and used them directly as clonospecific probes. The combination of PCR technology and hybridization to clonospecific probes permitted the detection of leukemia DNA at dilution of 1:100,000 in all five cases. Moreover, we were able to investigate one of the ALL patients 11 months after achieving continuous complete remission. Conventional Southern blot analysis failed to detect rearranged TCR genes at this stage. However, residual leukemic cells could readily be detected by PCR technique. We conclude that the strategy proposed here is a very sensitive tool to detect minimal residual disease in a significant proportion of human lymphoid neoplasias.
Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses (2012)

The induction of persistent intraepithelial CD8+ T cell responses may be key to the development of vaccines against mucosally transmitted pathogens, particularly for sexually transmitted diseases. Here we investigated CD8+ T cell responses in the female mouse cervicovaginal mucosa after intravaginal immunization with human papillomavirus vectors (HPV pseudoviruses) that transiently expressed a model antigen, respiratory syncytial virus (RSV) M/M2, in cervicovaginal keratinocytes. An HPV intravaginal prime/boost with different HPV serotypes induced 10-fold more cervicovaginal antigen-specific CD8+ T cells than priming alone. Antigen-specific T cell numbers decreased only 2-fold after 6 months. Most genital antigen-specific CD8+ T cells were intra- or subepithelial, expressed αE-integrin CD103, produced IFN-γ and TNF-α, and displayed in vivo cytotoxicity. Using a sphingosine-1-phosphate analog (FTY720), we found that the primed CD8+ T cells proliferated in the cervicovaginal mucosa upon HPV intravaginal boost. Intravaginal HPV prime/boost reduced cervicovaginal viral titers 1,000-fold after intravaginal challenge with vaccinia virus expressing the CD8 epitope M2. In contrast, intramuscular prime/boost with an adenovirus type 5 vector induced a higher level of systemic CD8+ T cells but failed to induce intraepithelial CD103+CD8+ T cells or protect against recombinant vaccinia vaginal challenge. Thus, HPV vectors are attractive gene-delivery platforms for inducing durable intraepithelial cervicovaginal CD8+ T cell responses by promoting local proliferation and retention of primed antigen-specific CD8+ T cells.
Identifying Architectural Bad Smells (2009)

Certain design fragments in software architectures can have a negative impact on system maintainability. In this paper, we introduce the concept of architectural "bad smells," which are frequently recurring software designs that can have non-obvious and significant detrimental effects on system lifecycle properties. We define architectural smells and differentiate them from related concepts, such as architectural antipatterns and code smells. We also describe four representative architectural smells we encountered in the context of reverse-engineering eighteen grid technologies and refactoring one large industrial system.
Fluorescence Resonance Energy Transfer Analysis of Ribozyme Kinetics Reveals the Mode of Action of a Facilitator Oligonucleotide (1996)

A defining characteristic of catalysts is the rate at which they can process multiple copies of substrate. In the case of synthetic hammerhead ribozymes that cleave an RNA sequence, binding of the ribozyme to the substrate and products is through base-paired duplexes. The kinetics of formation and dissociation of these duplexes can determine the turnover of the ribozyme. We have followed these processes in real time by using fluorescent labels that can interact through fluorescence resonance energy transfer (FRET). This approach has been used to identify the rate-limiting steps for a particular ribozyme and to reveal how turnover was improved by a facilitator oligonucleotide. It was found that dissociation of the ribozyme-substrate complex is faster than cleavage to products. Hence, to undergo cleavage, most substrate molecules must interact with a ribozyme more than once. In the presence of a facilitator oligonucleotide, the complex is stabilized so that cleavage is faster than dissociation. Under these circumstances, cleavage of the substrate becomes the most likely outcome following binding to the ribozyme.