gebhart/patrepeval huggingface dataset:
Nonclassical nicotine antagonists (1975)

A series of "nonclassical" nicotine antagonists was synthesized and compared to the "classical" nicotine antagonist, hexamethonium, by means of the isolated guinea pig atria preparation. 2 was found to be the most potent, followed by hexamethonium and the other antagonists. With the exception of 5, the bisquaternary compounds 1-3 and 7-9 were found to be more potent than the monoquaternary compounds 4, 6, and 10-12. Within a series of compounds (1-6 or 7-12), those compounds possessing two phenyl rings proved to be more potent than those possessing one or three phenyl rings. These and other aspects of the structure-activity relationship of this class of compounds are discussed.
Assessment of biocompatibility of 3D printed photopolymers using zebrafish embryo toxicity assays (2015)

3D printing has emerged as a rapid and cost-efficient manufacturing technique to enable the fabrication of bespoke, complex prototypes. If the technology is to have a significant impact in biomedical applications, such as drug discovery and molecular diagnostics, the devices produced must be biologically compatible to enable their use with established reference assays and protocols. In this work we demonstrate that we can adapt the Fish Embryo Test (FET) as a new method to quantify the toxicity of 3D printed microfluidic devices. We assessed the biocompatibility of four commercially available 3D printing polymers (VisiJetCrystal EX200, Watershed 11122XC, Fototec SLA 7150 Clear and ABSplus P-430), through the observation of key developmental markers in the developing zebrafish embryos. Results show all of the photopolymers to be highly toxic to the embryos, resulting in fatality, although we do demonstrate that post-printing treatment of Fototec 7150 makes it suitable for zebrafish culture within the FET.
A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas (2011)

Our results highlight important discrepancies between the numbers of CTC enumerated by both techniques. These differences depend mostly on the tumour type. These results suggest that technologies limiting CTC capture to EpCAM-positive cells, may present important limitations, especially in patients with metastatic lung carcinoma.
6. Intractable Chronic Constipation (2013)

便秘は国民の約3割が罹患している「大衆病」であるにもかかわらず，正しい病態理解に基づいた適切な治療が行われないことが多い．食物繊維の多量摂取で逆に症状が悪化するタイプの便秘も存在する．腸管拡張を伴わない「機能性便秘」には結腸通過時間正常型，遅延型，排泄障害型の3タイプが存在し，さらに腸管の病的拡張を伴う難治性便秘として慢性偽性腸閉塞などがある．これらの病態をよく把握し治療に臨むことが肝要である．
Mechanisms Controlling the Function and Life Span of the Corpus Luteum (2000)

The primary function of the corpus luteum is secretion of the hormone progesterone, which is required for maintenance of normal pregnancy in mammals. The corpus luteum develops from residual follicular granulosal and thecal cells after ovulation. Luteinizing hormone (LH) from the anterior pituitary is important for normal development and function of the corpus luteum in most mammals, although growth hormone, prolactin, and estradiol also play a role in several species. The mature corpus luteum is composed of at least two steroidogenic cell types based on morphological and biochemical criteria and on the follicular source of origin. Small luteal cells appear to be of thecal cell origin and respond to LH with increased secretion of progesterone. LH directly stimulates the secretion of progesterone from small luteal cells via activation of the protein kinase A second messenger pathway. Large luteal cells are of granulosal cell origin and contain receptors for PGF(2alpha) and appear to mediate the luteolytic actions of this hormone. If pregnancy does not occur, the corpus luteum must regress to allow follicular growth and ovulation and the reproductive cycle begins again. Luteal regression is initiated by PGF(2alpha) of uterine origin in most subprimate species. The role played by PGF(2alpha) in primates remains controversial. In primates, if PGF(2alpha) plays a role in luteolysis, it appears to be of ovarian origin. The antisteroidogenic effects of PGF(2alpha) appear to be mediated by the protein kinase C second messenger pathway, whereas loss of luteal cells appears to follow an influx of calcium, activation of endonucleases, and an apoptotic form of cell death. If the female becomes pregnant, continued secretion of progesterone from the corpus luteum is required to provide an appropriate uterine environment for maintenance of pregnancy. The mechanisms whereby the pregnant uterus signals the corpus luteum that a conceptus is present varies from secretion of a chorionic gonadotropin (primates and equids), to secretion of an antiluteolytic factor (domestic ruminants), and to a neuroendocrine reflex arc that modifies the secretory patterns of hormones from the anterior pituitary (most rodents).
Peroxides of elements other than carbon. Part XV. Autoxidation of the epimeric trinorbornylboranes (1969)

Three epimeric mixtures of trinorbornylboranes have been prepared, in which the percentages of exo- and endo-norbornyl groups are 99·2 and 0·8%, 66 and 34%, and 14 and 86%, respectively. All three react with oxygen to give norbornylbis(norbornylperoxy)borane containing about 76%exo- and 24%endo-norbornyl–oxygen links, and the reactions are inhibited by galvinoxyl, copper NN-dibutyldithiocarbamate, and phenothiazine. It is proposed that the autoxidations follow a homolytic chain mechanism involving a common norbornyl radical.
The Economic Impact of Diabetes (1998)

In assessing the economic impact of diabetes for a population, several factors should be considered, including the incidence and prevalence of the disease, the level of development of the health care system, and the population's overall level of economic development. Two different approaches have been used to address the economic impact of an increasing incidence of diabetes. The first approach uses disability-adjusted life-years (DALYs) to measure intangible costs associated with diabetes. It combines the number of healthy life-years lost as a result of early mortality with those lost because of disability. The second approach, which has been used more frequently, is the cost-of-illness approach, which includes the concepts of direct, indirect, and intangible costs. A study conducted by the World Bank found that of the 1,362 million DALYs lost to all illnesses in 1990, 7.97 million DALYs were lost because of diabetes. In a 1992 study that assessed the direct costs of treating diabetes in the U.S., the American Diabetes Association used the cost-of-illness approach and found that the estimated total expenditure for 1 year was $45.2 billion. The 1994 epidemiological studies by Zimmet and the World Health Organization include estimates of increased prevalence of diabetes resulting from an increase in population. Estimates of the global cost of diabetes based on these studies reveal that diabetes accounts for 2-3% of the total health care budget in every country; therefore, an increase in diabetes incidence and prevalence translates into a significant economic impact.
Misimpressions We Need to Extinguish (2002)

Networks dominate today’s computing landscape and commercial technical protection is lagging behind attack technology. As a result, protection programme success depends more on prudent management decisions than on the selection of technical safeguards. Managing Network Security takes a management view of protection and seeks to reconcile the need for security with the limitations of technology.
Marrow-derived heparan sulfate proteoglycan mediates the adhesion of hematopoietic progenitor cells to cytokines. (1995)

Heparan sulfate proteoglycan (HS-PG), an important component of the human bone marrow extracellular matrix (ECM), is believed to influence hematopoietic progenitor cell development by binding and localizing growth factors to specific niches within the hematopoietic microenvironment. We utilized a model ECM system, which uses immobilized ECM proteins and/or cytokines and bone marrow populations enriched for human hematopoietic stem cell (HSC), to assess the effects of HS-PG on the development of primitive hematopoietic progenitor cells. HS-PG alone failed to bind hematopoietic progenitor cells cloned from bone marrow CD34+CD15-HLA-DR- cells, which are enriched for HSC. HS-PG alone failed to function as a mitogen. In sharp contrast, the interaction of HS-PG with either growth factors (interleukin-3 [IL-3] or stem cell factor/Kit ligand [KL] or an ECM protein (thrombospondin [TSP]) markedly influenced progenitor cell adherence. The binding of either IL-3 or KL to HS-PG resulted in a two-fold increase in attachment of the colony-forming unit-granulocyte/macrophage (CFU-GM), a 1.5-fold increase in attachment of the burst-forming unit-erythroid (BFU-E) and the high-proliferative-potential colony-forming cell (HPP-CFC), and a two- to three-fold increase in attachment of the colony-forming unit-granulocyte/erythroid/macrophage/megakaryocyte (CFU-GEMM) compared to localized growth factor alone. Attachment of the BFU-megakaryocyte (BFU-MK), however, was slightly reduced by the interaction of either IL-3 or KL with HS-PG. The interaction of HS-PG with TSP resulted in a two-fold increase in CFU-GM and CFU-GEMM attachment, while the attachment of BFU-E, HPP-CFC, and BFU-MK was unaltered. We conclude that HS-PG cooperatively interacts with both growth factors and ECM proteins to augment progenitor cell localization within the hematopoietic microenvironment.
Astrocyte Mitogen Inhibitor Related to Epidermal Growth Factor Receptor (1988)

Epidermal growth factor (EGF) is a well-characterized polypeptide hormone with diverse biological activities, including stimulation of astrocyte division. A soluble astrocyte mitogen inhibitor, immunologically related to the EGF receptor, is present in rat brain. Injury to the brain causes a time-dependent reduction in the levels of this inhibitor and the concomitant appearance of EGF receptor on the astrocyte surface. Intracerebral injection of antibody capable of binding the inhibitor caused the appearance of numerous reactive astrocytes. EGF receptor-related inhibitors may play a key role in the control of glial cell division in both normal and injured brain.
Enantio‐ and Diastereoselective Catalytic Mannich‐Type Reaction of a Glycine Schiff Base Using a Chiral Two‐Center Phase‐Transfer Catalyst (2005)

Optically active α,β-diamino acids are prepared under asymmetric phase-transfer reaction conditions from a glycine Schiff base and N-protected imines with a tartrate-derived diammonium salt (TaDiAS) as the phase-transfer catalyst (see scheme; Boc=tert-butoxycarbonyl). Chemoselective deprotection of the N atoms allows straightforward transformations of the α,β-diamino acid products to be carried out.
Manganese(II), iron(II), cobalt(II), and copper(II) complexes of an extended inherently chiral tris-bipyridyl cage (2006)

Manganese(II), iron(II), cobalt(II), and copper(II) derivatives of two inherently chiral, Tris(bipyridyl) cages (L and L') of type [ML]-(PF(6))(2)(solvent)(n) and [FeL'](ClO(4))(2) are reported, where L is the hexa-tertiary butyl-substituted derivative of L'. These products were obtained by using the free cage and metal template procedures; the latter involved the reductive amination of the respective Tris-dialdehyde precursor complexes of iron(II), cobalt(II), or nickel(II). Electrochemical, EPR, and NMR studies have been used to probe the nature of the individual complexes. X-ray structures of the manganese(II), iron(II), and copper(II) complexes of L and the iron(II) complex of L' are presented; these are compared with the previously reported structures of the corresponding nickel(II) complex and metal-free cage (L). In each complex the metal cation occupies the cage's central cavity and is coordinated to six nitrogens from the three bipyridyl groups. The cations [MnL](2+) and [FeL](2+) are isostructural but both exhibit a different arrangement of the bound cage to that observed in the corresponding nickel(II) and copper(II) complexes. The latter have an exo-exo arrangement of the bridgehead nitrogen lone pairs, with the metal inducing a triple helical twist that extends approximately 22 A along the axial length of each complex. In contrast, [MnL](2+) and [FeL](2+) have their terminal nitrogen lone pairs directed endo, causing a significant change in the configuration of the bound ligand. In [FeL'](2+), the cage has both bridgehead nitrogen lone pairs orientated exo. Semiempirical calculations indicate that the observed endo-endo and exo-exo arrangements are of comparable energy.
Insights into Phenylalanine Derivatives Recognition of VLA-4 Integrin:  From a Pharmacophoric Study to 3D-QSAR and Molecular Docking Analyses (2004)

The very late antigen-4 (VLA-4), also known as integrin alpha4beta1, is expressed on monocytes, T- and B-lympohocytes, basophils, and eosinophils and is involved in the massive recruitment of granulocytes in different pathological conditions such as multiple sclerosis and asthma. VLA-4 interacts with its endogenous ligand VCAM-1 during chronic inflammation, and blockade of VLA-4 /VCAM-1 interaction is a potential target for immunosuppression. Two classes of VLA-4 antagonists have so far been reported: beta-amino acid derivatives containing a diaryl urea moiety (BIO-1211) and phenylalanine derivatives (TR-14035). With the aim of clarifying the structural basis responsible for VLA-4 recognition by phenylalanine derivatives, we developed a combined computational study on a set of 128 antagonists available through the literature. Our computational approach is composed of three parts. (i) A VCAM-1 based pharmacophore was constructed with a restricted number of phenylalanine derivatives to identify the region of the protein that resembles synthetic antagonists. The pharmacophore was instrumental in constructing an alignment of a set of 128 compounds. This alignment was exploited to build a pseudoreceptor model with the RECEPTOR program. (ii) 3D-QSAR analysis was carried out on the computed electrostatic and steric interaction energies with the pseudoreceptor surface. The 3D-QSAR analysis yielded a predictive model able to explain much of the variance of the 128 antagonists. (iii) A homology modeling study of the headpiece of VLA-4 based on the crystal structure of alphavbeta3 was performed. Docking experiments of TR-14035 into the binding site of VLA-4 aided the interpretation of the 3D-QSAR model. The obtained results will be fruitful for the design of new potent and selective antagonists of VLA-4.
Comparison of the Signaling Abilities of the Drosophila and Human Insulin Receptors in Mammalian Cells (1995)

Chimeric receptors encoding either the whole or a portion of the cytoplasmic domain of the drosophila insulin receptor (IR) with the extracellular domain of the human IR were expressed either transiently in COS cells or stably in Chinese hamster ovary cells and compared with the wild-type human IR. All three receptors bound insulin equally and exhibited an insulin-activated tyrosine kinase activity. The ability of the drosophila cytoplasmic domain to mediate the tyrosine phosphorylation of insulin receptor substrate 1, stimulate cell proliferation, and activate MAP kinase was found to be indistinguishable from that of the human IR. The chimeric drosophila receptors did not bind more phosphatidylinositol 3-kinase than the human IR, despite containing a C-terminal extension with potential tyrosine phosphorylation sites in the motif recognized by the SH2 domain of this enzyme. Thus, the essential signal-transducing abilities of the IR appear to have been conserved from invertebrates to mammals, despite the considerable differences in the sequences of these receptors.
Isolation and characterization of a sperm-specific gene family in the nematode Caenorhabditis elegans. (1984)

The major sperm protein (MSP) of the nematode Caenorhabditis elegans is a low-molecular-weight (15,000) basic protein implicated in the pseudopodial movement of mature spermatozoa. Its synthesis occurs in a specific region of the gonad and is regulated at the level of transcription (M. Klass and D. Hirsh, Dev. Biol. 84:299-312, 1981; S. Ward and M. Klass, Dev. Biol. 92:203-208, 1982; Klass et al., Dev. Biol. 93:152-164, 1982). A developmentally regulated gene family has been identified that codes for this MSP. Whole genomic blots, as well as analysis of genomic clone banks, indicate that there are between 15 and 25 copies of the MSP gene in the nematode genome. Southern blot analysis also indicates that there is no rearrangement or amplification within the MSP gene family during development. No evidence was found of methylation at various restriction sites surrounding the MSP gene family, and similarly, no correlation between methylation and expression was observed. Three distinct members of this MSP gene family have been cloned, and their nucleotide sequences have been determined. Differential screening of a cDNA clone bank made from polyadenylated mRNA from adult males yielded 45 male-specific clones, 32 of which were clones of MSP genes. One of these cDNA clones was found to contain the entire nucleotide sequence for the MSP, including part of the 5' leader and all of the 3' trailing sequence. Genomic clones bearing copies of the MSP genes have been isolated. At least one of the members of this gene family is a pseudogene. Another member of the MSP gene family that has been cloned from genomic DNA contains the entire uninterrupted structural sequence for the MSP in addition to a 5' flanking sequence containing a promoter-like region with the classic TATA box, a sequence resembling the CAAT box, and a putative ribosome-binding sequence. The 3' trailing sequences of the genomic and the cDNA clones contain an AATAAA polyadenylation site.
Innovative Design Allows Construction Of Level 3 Or Level 4 Junction Using The Same Platform (2002)

Abstract The simple and most economical multilateral option in the production of heavy oil with optimum solids control is to employ either level 3 or level 4 junctions to access and drain oil bearing sand bodies. This paper presents an innovative junction design which when fully deployed, can be left as a level 3 construction, or it can be turned in to level 4 by conventionally cementing the junction. In practice the isolation provided with the level 3 construction far exceeds the capabilities of conventional alternatives, and when cemented as a level 4, provides a junction with stability beyond that afforded by conventional methods. In either scenario, access to the main bore below the junction and to the lateral bore is maintained. Once the junction is in place, conventional completion equipment can be run after drilling the lateral to facilitate the production. In addition, this innovative junction offers other advantages. Among those are, (1) Milling or washover of excess liner is not required when constructing a level 4 junction because there is no excess liner left in the main bore during the junction construction. (2) The lateral liner can be deployed simultaneously with the junction for both level 3 and level 4 junctions. (3) The platform allows full re-entry capability into main and lateral bores in a single or stacked junction configuration. The paper will also discuss in detail, recent field installations and developments of this innovative design in level 4 complexity in 9-5/8" 40 lb/ft casing. Major system components and their functions are described, as well as running procedures and lessons learned.
Review: Durability and Degradation Issues of PEM Fuel Cell Components (2008)

Abstract Besides cost reduction, durability is the most important issue to be solved before commercialisation of PEM Fuel Cells can be successful. For a fuel cell operating under constant load conditions, at a relative humidity close to 100% and at a temperature of maximum 75 °C, using optimal stack and flow design, the voltage degradation can be as low as 1–2 μV·h. However, the degradation rates can increase by orders of magnitude when conditions include some of the following, i.e. load cycling, start–stop cycles, low humidification or humidification cycling, temperatures of 90 °C or higher and fuel starvation. This review paper aims at assessing the degradation mechanisms of membranes, electrodes, bipolar plates and seals. By collecting long‐term experiments as well, the relative importance of these degradation mechanisms and the operating conditions become apparent.
Chemistry of the Hexahydropyrrolo[2,3-b]indoles:  Configuration, Conformation, Reactivity, and Applications in Synthesis (2007)

The stereoselective formation of 2-endo-substituted hexahydropyrrolo[2,3-b]indoles from 2-substituted tryptamine derivatives, especially tryptophan, is discussed. Parallels are drawn with the formation of related heterocyclic systems, such as the hexahydrofurano[2,3-b]benzofurans, in which the thermodynamic preference of a substituent at the 2-position is also for the endo-configuration. Functionalization of tryptophan-derived hexahydropyrroloindoles at positions 2-, 3-, and 3a- is discussed with special emphasis on the 2-position, at which both radical and nucleophilic reactions take place preferentially on the endo-face of the diazabicyclo[3.3.0]octane system. The kinetic and thermodynamic preference for the 2-endo-position is considered in terms of the minimization of torsional strain, and parallels are drawn to the Woerpel model for the reactivity of analogous five-membered cyclic oxacarbenium ions. The use of the tryptophan-derived hexahydro[2,3-b]pyrroloindoles in the stereocontrolled synthesis of amino acids and alkaloids is presented.
Energy Components During the Triaxial Cell and Direct Shear Tests (1964)

Synopsis The components of energy loss during a triaxial cell test are examined critically. It is shown that the stress dilatancy equation may be derived by inserting a modified cell pressure into the Bishop energy correction. The physical reason for this is discussed and the correct solution is derived in three different ways. In view of this correlation with previous thought the components of the Roscoe energy balance are discussed. The stress dilatancy equation for the triaxial cell extension test is also derived, making use of energy components. The expression for the rate of internal work absorbed in friction due solely to dilation in a direct shear is shown to be similar in form to that in the triaxial cell test. Les composantes de perte d'énergie pendant un essai de cellule triaxial sont examinées critiquement. On montre que l'équation de dilatabilité des contraintes peut être dérivée en insérant une pression de cellule modifiée dans la correction d'énergie de Bishop. La raison physique de cette opération est discutée et la solution exacte est dérivée de trois manières différentes. En raison de cette corrélation avec l'opinion précédente les composantes de l'équilibre d'énergie de Roscoe sont discutées. L'équation de dilatabilité des contraintes pour l'essai de dilatation de la cellule triaxiale est aussi dérivée, en faisant usage des composantes d'énergie. L'expression pour la proportion de travail interne absorbée par le frottement uniquement dû à la dilatation dans un cisaillement direct, est représentée comme étant semblable comme forme à celle de l'essai de cellule triaxiale.