gebhart/patrepeval huggingface dataset:
HER-2 amplification impedes the antiproliferative effects of hormone therapy in estrogen receptor-positive primary breast cancer. (2001)

In experimental models, human epidermal growth factor receptor-2 (HER-2) amplification leads to estrogen independence and tamoxifen resistance in estrogen receptor (ER)-positive human breast cancer cells. Some but not all reports suggest an association between HER-2 positivity and hormone independence in breast cancer patients. This study aimed to evaluate the antiproliferative effects of endocrine therapy in HER-2-positive/ER-positive primary human breast cancer. The effect on proliferation (Ki67) of hormone therapy was assessed at 2 weeks and/or 12 weeks in biopsies from 115 primary breast cancers with ER-positive tumors. The patients took part in one of 3 neoadjuvant trials of hormonal therapy with a SERM (tamoxifen or idoxifene) or an aromatase inhibitor (anastrozole or vorozole). HER-2 status was assessed by immunocytochemistry and fluorescence in situ hybridization (FISH). Fifteen patients were defined as HER-2 positive by both immunohistochemistry and FISH, with the remaining 100 patients HER-2 negative. Geometric mean Ki67 levels were substantially higher in HER-2-positive than HER-2-negative tumors (27.7% versus 11.5%, respectively; P = 0.003). In HER-2-negative patients, Ki67 was reduced by 62 and 71% at 2 and 12 weeks, respectively (P < 0.0001 for both), but HER-2-positive patients showed no significant fall. The proportional change in Ki67 was significantly different between HER-2-positive and -negative patients (P = 0.014 at 2 weeks; P = 0.047 at 12 weeks). Mean ER levels were lower in the HER-2-positive patients (P = 0.06) but the change in Ki67 was impeded even in those with high ER. Apoptotic index was reduced by 30% at 2 weeks in the HER-2-negative group. However, there were no statistically significant differences in apoptotic index between the groups. It is concluded that ER-positive/HER-2-positive primary breast carcinomas show an impeded antiproliferative response to endocrine therapy that nonetheless may vary between individual treatments. This together with high baseline proliferation is likely to translate to poor clinical response.
Substitution for PCP, disruption of prepulse inhibition and hyperactivity induced by N-methyl-D-aspartate receptor antagonists: preferential involvement of the NR2B rather than NR2A subunit. (2003)

The non-competitive NMDA receptor antagonist phencyclidine (PCP) is known to produce a discriminative stimulus in rats. The first aim of the present study was to investigate which NMDA receptor subtype(s) is involved in this effect of PCP. Rats were trained to discriminate PCP (2 mg/kg; i.p.) from saline in a two lever operant task. The NMDA channel blocker, (+)MK-801 (0.1 mg/kg; i.p.) and the competitive NMDA receptor antagonist SDZ 220-581 (3 mg/kg; i.p.) produced 76% of PCP-lever selection (ED50=0.045 and 2 mg/kg, respectively), whereas their respective inactive enantiomers (-)MK-801 (0.025-0.1 mg/kg) and SDZ 221-653 (2-5 mg/kg) induced less than 30% of PCP-appropriate responding. Another competitive NMDA antagonist, SDZ EAB-515 (30 mg/kg; i.p.), induced 63% of PCP-lever responding (ED50=23.48 mg/kg). The selective antagonist of NMDA receptors containing the NR1A/NR2B-subunits Ro 25-6981 (20 mg/kg; i.p.) resulted in a complete substitution (more than 80% of PCP-lever selection) for PCP (ED50=8.59 mg/kg). In contrast, the NR1A/NR2A NMDA receptor-preferring antagonist NVP-AAM077 (2-10 mg/kg; i.p.) failed to produce PCP-like discriminative stimuli. At high doses SDZ 220-581 (ED50=2.44), NVP-AAM077 (ED50=8.33) and SDZ EAB-515 (ED50=25.81) decreased the performance of the rats in this operant task. The ability of these NMDA receptor antagonists to disrupt the prepulse inhibition (PPI) of the startle response and to alter locomotor activity was also studied. PCP (0.5-2 mg/kg; s.c.), SDZ 220-581 (0.5-5 mg/kg; s.c.), SDZ EAB-515 (1-30 mg/kg; i.p.) and Ro 25-6981 (5-20 mg/kg; i.p.) disrupted PPI and at high doses produced hyperlocomotion. In contrast, NVP-AAM077 (5-20 mg/kg; i.p.) did not disrupt PPI and reduced locomotor activity. In conclusion, it appears that the NMDA receptor containing the NR2B, rather than the NR2A subunit, may play a major role in the PCP-like discriminative stimulus. In addition, sensory motor gating disturbances associated with NMDA antagonists do not seem to result from a blockade of NR1/NR2A-containing NMDA receptors.
Phylogenetic Analysis of Rhizobia and Agrobacteria Based on 16S rRNA Gene Sequences (1993)

The phylogenetic relationships of members of the genera Rhizobium, Agrobacterium, Bradyrhizobium, and Azorhizobium were studied by direct sequencing of their amplified 16S rRNA genes. Comparative analysis of the sequence data confirmed that the genera Bradyrhizobium and Azorhizobium belong to distinct phylogenetic lineages. The genera Rhizobium and Agrobacterium were found to be phylogenetically heterogeneous, and several subgroupings in which Rhizobium and Agrobacterium species were intermixed were evident. The present findings show that the genus and species definitions of these organisms are in need of revision. Different possibilities for this are discussed in the light of sequencing data.
Bone Overgrowth-associated Mutations in the LRP4 Gene Impair Sclerostin Facilitator Function (2011)

Humans lacking sclerostin display progressive bone overgrowth due to increased bone formation. Although it is well established that sclerostin is an osteocyte-secreted bone formation inhibitor, the underlying molecular mechanisms are not fully elucidated. We identified in tandem affinity purification proteomics screens LRP4 (low density lipoprotein-related protein 4) as a sclerostin interaction partner. Biochemical assays with recombinant proteins confirmed that sclerostin LRP4 interaction is direct. Interestingly, in vitro overexpression and RNAi-mediated knockdown experiments revealed that LRP4 specifically facilitates the previously described inhibitory action of sclerostin on Wnt1/β-catenin signaling. We found the extracellular β-propeller structured domain of LRP4 to be required for this sclerostin facilitator activity. Immunohistochemistry demonstrated that LRP4 protein is present in human and rodent osteoblasts and osteocytes, both presumed target cells of sclerostin action. Silencing of LRP4 by lentivirus-mediated shRNA delivery blocked sclerostin inhibitory action on in vitro bone mineralization. Notably, we identified two mutations in LRP4 (R1170W and W1186S) in patients suffering from bone overgrowth. We found that these mutations impair LRP4 interaction with sclerostin and its concomitant sclerostin facilitator effect. Together these data indicate that the interaction of sclerostin with LRP4 is required to mediate the inhibitory function of sclerostin on bone formation, thus identifying a novel role for LRP4 in bone.
Power Transmission Losses in V-Belt Drives Part 2: Effects of Small Pulley Radii (1987)

Run-in AV10 wrapped, raw-edged and cogged V-belts have been used to transmit power between pulleys of equal radii R equal to 51, 36 and 21 mm. Separate measurements of the torque and angular speed losses between the pulleys have shown that these are approximately proportional to 1/R and 1/R 2 respectively and are also greater than expected from current theories. The maximum useful belt tension ratio fell from 21 to 5 as R was reduced from 51 to 21 mm. A dimensionless belt deformation parameter (gEI/R 4 ) 1/2 , arising from a simplified analysis of torque loss, has been found empirically to correlate with both torque loss and the speed loss in excess of that expected from belt extension and radial compliance. Subsidiary tests with thick flat belts on cylindrical pulleys have shown their power losses to be unexpectedly close to those of V-belts of similar cross-sectional area, suggesting that those V-belt losses usually attributed to wedging in the pulley groove are of more general origin. It is speculated that belt carcass warping or shearing distortions must be considered to explain losses on small-radii pulleys.
Bubble development in a polymeric resin under vacuum (2012)

Abstract Understanding the gas diffusion and evaporation behavior in a polymeric resin under vacuum is of great importance because many types of polymer and composite products are manufactured by applying a vacuum to the production system. This article proposes a theoretical model that can describe bubble growth under vacuum by combining the mechanisms of gas diffusion and evaporation. To confirm such a model, we carried out experimental analyses including evaporation experiments with a bell jar or a tube as well as vacuum‐assisted resin transfer molding (VARTM). Particularly in the VARTM process, it was identified that many bubbles were nucleated and grew at the fiber‐matrix interface due to the applied vacuum pressure. Those results suggest that more attention should be paid to vacuum‐assisted material processing to prevent bubbles from existing in the final products. POLYM. ENG. SCI., 2012. © 2012 Society of Plastics Engineers
Type I IFN Induced by Adenovirus Serotypes 28 and 35 Has Multiple Effects on T Cell Immunogenicity (2012)

Recombinant adenovirus (rAd) vectors are being investigated as vaccine delivery vehicles in preclinical and clinical studies. rAds constructed from different serotypes differ in receptor usage, tropism, and ability to activate cells, aspects of which likely contribute to their different immunogenicity profiles. In this study, we compared the infectivity and cell stimulatory capacity of recombinant adenovirus serotype 5 (rAd5), recombinant adenovirus serotype 28 (rAd28), and recombinant adenovirus serotype 35 (rAd35) in association with their respective immunogenicity profiles. We found that rAd28 and rAd35 infected and led to the in vitro maturation and activation of both human and mouse dendritic cells more efficiently compared with rAd5. In stark contrast to rAd5, rAd28 and rAd35 induced production of IFN-α and stimulated IFN-related intracellular pathways. However, the in vivo immunogenicity of rAd28 and rAd35 was significantly lower than that of rAd5. Deletion of IFN-α signaling during vaccination with rAd28 and rAd35 vectors increased the magnitude of the insert-specific T cell response to levels induced by vaccination with rAd5 vector. The negative impact of IFN-α signaling on the magnitude of the T cell response could be overcome by increasing the vaccine dose, which was also associated with greater polyfunctionality and a more favorable long-term memory phenotype of the CD8 T cell response in the presence of IFN-α signaling. Taken together, our results demonstrate that rAd-induced IFN-α production has multiple effects on T cell immunogenicity, the understanding of which should be considered in the design of rAd vaccine vectors.
Mechanistic studies on bovine cytosolic 5′‐nucleotidase II, an enzyme belonging to the HAD superfamily (2004)

Cytosolic 5'-nucleotidase/phosphotransferase specific for 6-hydroxypurine monophosphate derivatives (cN-II), belongs to a class of phosphohydrolases that act through the formation of an enzyme-phosphate intermediate. Sequence alignment with members of the P-type ATPases/L-2-haloacid dehalogenase superfamily identified three highly conserved motifs in cN-II and other cytosolic nucleotidases. Mutagenesis studies at specific amino acids occurring in cN-II conserved motifs were performed. The modification of the measured kinetic parameters, caused by conservative and nonconservative substitutions, suggested that motif I is involved in the formation and stabilization of the covalent enzyme-phosphate intermediate. Similarly, T249 in motif II as well as K292 in motif III also contribute to stabilize the phospho-enzyme adduct. Finally, D351 and D356 in motif III coordinate magnesium ion, which is required for catalysis. These findings were consistent with data already determined for P-type ATPases, haloacid dehalogenases and phosphotransferases, thus suggesting that cN-II and other mammalian 5'-nucleotidases are characterized by a 3D arrangement related to the 2-haloacid dehalogenase superfold. Structural determinants involved in differential regulation by nonprotein ligands and redox reagents of the two naturally occurring cN-II forms generated by proteolysis were ascertained by combined biochemical and mass spectrometric investigations. These experiments indicated that the C-terminal region of cN-II contains a cysteine prone to form a disulfide bond, thereby inactivating the enzyme. Proteolysis events that generate the observed cN-II forms, eliminating this C-terminal portion, may prevent loss of enzymic activity and can be regarded as regulatory phenomena.
Monolayer-level controlled incorporation of nitrogen at Si–SiO2 interfaces using remote plasma processing (1999)

We demonstrate three different ways to incorporate nitrogen at Si–SiO2 interfaces: (i) an O2/He plasma oxidation of the Si surface followed by an N2/He plasma nitridation, (ii) an N2/He plasma nitridation of the Si surface, and (iii) a Si3N4 film deposition on to the Si surface. The two-step interface formation, the O2/He plasma oxidation followed by the N2/He plasma nitridation, is shown to yield significantly better interface device properties than the other two approaches. These differences in interface properties are explained by an application of constraint theory based on comparisons of the average bonding coordination of the dielectric layer at the interface with the Si substrate.
CURRENT APPROACHES TO ASSESSING RISK IN MAINTENANCE AND INSPECTION (2002)

As researchers, designers, operators, and managers of complex, high-risk operations, we share an interest in human performance tools that can help us assess and manage risk. Through effective risk management, we seek to achieve the highest levels of operational and personal safety as a top priority. At the same time, however, operations must prove themselves efficient and effective in a time of dwindling resources and an unpredictable economy. In light of these conditions, we, more than ever, need reliable and valid tools to assess risk so that resources can be managed effectively and the balance of safety and performance is optimized. I will be describing several innovative approaches to risk that have been developing over the last five or six years. But first, I would like to introduce three types of risk in order to set up a context for describing these new approaches. The three risk types are 1) design risk, 2) process risk, and 3) the risk of human error. As their names suggest, they refer to different targets and serve different purposes although I will argue that they have been mixed and merged in a variety of helpful and unhelpful ways. In spite of the fact that the different risk types often share analysis tools, their distinct objectives and limitations should provide guidance for their best use. The new initiatives I will describe cross the boundaries of these risk types as they combine to create a more robust and expanded risk description.
Snapshots of Catalysis:  the Structure of Fructose-1,6-(bis)phosphate Aldolase Covalently Bound to the Substrate Dihydroxyacetone Phosphate<sup>,</sup> (2001)

Fructose-1,6-bis(phosphate) aldolase is an essential glycolytic enzyme found in all vertebrates and higher plants that catalyzes the cleavage of fructose 1,6-bis(phosphate) (Fru-1,6-P(2)) to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). Mutations in the aldolase genes in humans cause hemolytic anemia and hereditary fructose intolerance. The structure of the aldolase-DHAP Schiff base has been determined by X-ray crystallography to 2.6 A resolution (R(cryst) = 0.213, R(free) = 0.249) by trapping the catalytic intermediate with NaBH(4) in the presence of Fru-1,6-P(2). This is the first structure of a trapped covalent intermediate for this essential glycolytic enzyme. The structure allows the elucidation of a comprehensive catalytic mechanism and identification of a conserved chemical motif in Schiff-base aldolases. The position of the bound DHAP relative to Asp33 is consistent with a role for Asp33 in deprotonation of the C4-hydroxyl leading to C-C bond cleavage. The methyl side chain of Ala31 is positioned directly opposite the C3-hydroxyl, sterically favoring the S-configuration of the substrate at this carbon. The "trigger" residue Arg303, which binds the substrate C6-phosphate group, is a ligand to the phosphate group of DHAP. The observed movement of the ligand between substrate and product phosphates may provide a structural link between the substrate cleavage and the conformational change in the C-terminus associated with product release. The position of Glu187 in relation to the DHAP Schiff base is consistent with a role for the residue in protonation of the hydroxyl group of the carbinolamine in the dehydration step, catalyzing Schiff-base formation. The overlay of the aldolase-DHAP structure with that of the covalent enzyme-dihydroxyacetone structure of the mechanistically similar transaldolase and KDPG aldolase allows the identification of a conserved Lys-Glu dyad involved in Schiff-base formation and breakdown. The overlay highlights the fact that Lys146 in aldolase is replaced in transaldolase with Asn35. The substitution in transaldolase stabilizes the enamine intermediate required for the attack of the second aldose substrate, changing the chemistry from aldolase to transaldolase.
A human immunodeficiency caused by mutations in the PIK3R1 gene (2015)

The authors recently identified an error in the identification numbers assigned to patient samples that resulted in an incorrect clinical and immunological description of patient 4 (P4). The error did not affect the conclusions of the manuscript; however, the correct immunological profile is now included in the revised version of Table
Hybrids of [TSAO-T]−[Foscarnet]:  The First Conjugate of Foscarnet with a Non-nucleoside Reverse Transcriptase Inhibitor through a Labile Covalent Ester Bond (2004)

This paper describes the first example of combination of non-nucleoside reverse transcriptase inhibitors such as TSAO derivatives and foscarnet (PFA) in a single molecule through a labile covalent ester bond. The essential criteria in the design of these hybrids [TSAO-T]-[PFA] was to explore if the conjugation of foscarnet with the highly lipophilic TSAO derivative may facilitate the penetration of the conjugates through the cell membrane and if the hybrids escape extracellular hydrolysis and regenerate the parent inhibitors intracellulary. Several [TSAO-T]-[PFA] conjugates proved markedly inhibitory to HIV-1. Some of them also showed potent activity against PFA-resistant HIV-1 strains but fewer had detectable inhibitory activity against TSAO-resistant HIV-1 strains. These results indicated a pivotal role of the TSAO component of the hybrid but not the PFA component in the activity of the conjugates. Moreover, stability studies of the [TSAO-T]-[PFA] conjugates demonstrated that the compounds were stable in PBS whereas some of the conjugates regenerated the parent inhibitors in extracts from CEM cells.
Hand-held calculator assists in directional drilling control. Part 2 (1982)

This paper describes the process of calculating borehole sensor outputs using a program which simulates the measurement of magnetic and gravity fields. It presents figures showing the magnetic field projections on the principal axes, user instructions, a program listing of ''Sensors'' for an HP-41C programmable calculator with one extra memory module installed and connected to a printer, and example input and output data. This program can be modified to run on HP-67/HP-97 calculators. It can be stored and run along with the inverse program ''Angles'' for error analysis or other purposes since the program registers are separate.
Effects of core‐shell latex morphology on film forming behavior (1990)

Abstract A series of core‐and‐shell latex particles were made from methyl methacrylate/butyl acrylate copolymers. All latexes were almost monodisperse in particle size. The polymer hardness was varied by changing the methyl methacrylate/butyl acrylate ratio between the limits of 40/60 and 60/40 parts by weight. The minimum film temperatures(MFTs) of these particles were expected to vary with core and shell characteristics in the following order: soft/hard > medium/medium > hard/soft. In fact, this order was observed only if the shell thickness was greater than a certain minimum value that depends on the diameter of the core polymer. Thinner, softer shells on harder cores may require higher drying temperatures than thicker shells with the same composition because the former are required to deform more to produce void‐free films.
Concise Synthesis of Tryptanthrin Spiro Analogues with In Vitro Antitumor Activity Based on One-Pot, Three-Component 1,3-Dipolar Cycloaddition of Azomethine Ylides to Сyclopropenes (2018)

A simple, efficient and atom-economic method has been developed for the synthesis of complex alkaloid-like compounds with spiro-fused indolo[2,1-b]quinazoline and cyclopropa[a]pyrrolizine or 3-azabicyclo[3.1.0]hexane moieties. We have found that one-pot, three-component 1,3-dipolar cycloaddition reactions allow the desired products to be obtained from various cyclopropene derivatives with tryptanthrin-derived azomethine ylides generated in situ, in good to high yields and excellent diastereoselectivity. The possibility of ylide generation was exemplified by using α-amino acids (l-proline, l-4-thiazolidincarboxylic acid) and simplest peptides (dipeptide Gly-Gly, tripeptide Gly-Gly-Gly). Quantum chemical investigations indicate that the reaction proceeds through the S-shaped azomethine ylide, the interaction of which with cyclopropenes proceeds via a less sterically hindered endo-transition state. The antitumor activity of some of spiro-tryptanthrin derivatives against erythroleukemia (K562), cervical carcinoma (HeLa) and colon carcinoma (CT26) cell lines was evaluated in vitro by MTS-assay.
In vivo changes of nanoapatite crystals during bone reconstruction and the differences with native bone apatite (2019)

Hydroxyapatite (HA) plays an important role in clinical bone repair. However, it remains a challenge to accurately determine its changes during bone reconstruction and to identify its differences from native bone apatite. Here, terbium (Tb) doped uniform HA nanocrystals were implanted into bone tissue and compared with native bone apatite. These comparisons demonstrated the occurrence of compositional and structural alteration of the implanted HA nanocrystals, and their gradual degradation, during bone reconstruction. They also revealed notable differences between HA nanocrystals and bone apatite crystals in crystal size, distribution pattern, and state of existence in bone tissue. Although synthetic HA nanocrystals could osteointegrate with bone tissue, they still seemed to be treated as foreign material in this tissue and thus were gradually degraded. These findings can help to identify and rethink the function of synthetic apatite and bone apatite, which will benefit future design and application of biomimetic bone repair materials.