gebhart/patrepeval huggingface dataset:
Metabolism of thiabendazole and teratogenic potential of its metabolites in pregnant mice. (1987)

In connection with the teratogenic activity of thiabendazole (TBZ), the metabolic fate of 14C-TBZ in pregnant mice was studied by administration of the drug in olive oil and gum arabic as vehicles. Absorption of TBZ in the olive oil group occurred more rapidly than in the gum arabic group, and the maximum blood level in the former group was 7-fold higher than that in the latter group. 5-Hydroxylated TBZ (5-HY TBZ), its glucuronide and its sulfate were identified as urinary and fecal metabolites. A very small quantity of N-methyl TBZ was also identified for the first time in the urine and feces. The percentages of TBZ, 5-HY TBZ, and the glucuronide and sulfate of 5-HY TBZ in the urine were 12-15, 22-24, 28-29 and 30-31%, respectively. About 97% of the dose was excreted into the urine (60-62%) and the feces (34-37%) within 7 d in each group. In a limb bud cell culture system for the assay of teratogenic potential, the concentrations of TBZ, 5-HY TBZ and N-methyl TBZ necessary to reduce the amounts of cartilage proteoglycan by 50% were estimated to be about 0.09, 0.09 and 0.24 mM, respectively. However, the concentrations of 5-HY TBZ glucuronide and sulfate were over 2 mM. Consequently, teratogenesis caused by TBZ appeared to be induced by the high levels of direct-acting teratogens such as TBZ and 5-HY TBZ when olive oil was used as a vehicle.
Linear Resonance Compressor for Stirling-Type Cryocoolers Activated by Piezoelectric Stack-Type Elements (2015)

A novel type of a PZT- based compressor operating at mechanical resonance, suitable for pneumatically-driven Stirling-type cryocoolers was developed theoretically and built practically during this research. A resonance operation at relatively low frequency was achieved by incorporating the piezo ceramics into the moving part, and by reducing the effective piezo stiffness using hydraulic amplification. The detailed concept, analytical model and the test results of the preliminary prototype were reported earlier and presented at ICC17 [2]. A fine agreement between the simulations and experiments spurred development of the current actual compressor designed to drive a miniature Pulse Tube cryocooler, particularly our MTSa model, which operates at 103 Hz and requires an average PV power of 11 W, filling pressure of 40 Bar and a pressure ratio of 1.3. The paper concentrates on design aspects and optimization of the governing parameters. The small stroke to diameter ratio (about 1:10) allows for the use of a composite diaphragm instead of a clearance-seal piston. The motivation is to create an adequate separation between the working fluid and the buffer gas of the compressor, thus preventing possible contamination in the cryocooler. Providing efficiency and power density similar to those of conventional linear compressors, the piezo compressor may serve as a good alternative for cryogenic applications requiring extreme reliability and absence of magnetic field interference.
Temperature and stress dependences of the magnetostriction in ternary and quaternary Terfenol alloys (2000)

The magnetization and magnetostriction of a variety of Laves phase rods of TbxDyyHo1−x−yFe1.95 grown in the form of [112] oriented dendritic platelets were measured as a function of magnetic field H(−2200&amp;lt;H&amp;lt;2200 Oe), compressive stress (20, 30, and 40 MPa), and temperature T(−60&amp;lt;T&amp;lt;80 °C). Compared to Terfenol-D (Tb0.3Dy0.7Fe1.95), Ho containing alloys can have lower hysteresis with only slightly lower magnetostriction. Sample compositions were chosen both along a line of minimum near room-temperature anisotropy (Tb0.3Dy0.7Fe1.95–Tb0.20Dy0.22Ho0.58Fe1.95) and at Ho0.15 and Ho0.30 across the line.
CCR2 Signaling Contributes to Ischemia-Reperfusion Injury in Kidney (2003)

Examined were CCR2-deficient mice to clarify the contribution of macrophages via monocyte chemoattractant protein 1 (MCP-1 or CCL2)/CCR2 signaling to the pathogenesis of renal ischemia-reperfusion injury. Also evaluated was the therapeutic effects via the inhibition of MCP-1/CCR2 signaling with propagermanium (3-oxygermylpropionic acid polymer) and RS-504393. Renal artery and vein of the left kidney were occluded with a vascular clamp for 60 min. A large number of infiltrated cells and marked acute tubular necrosis in outer medulla after renal ischemia-reperfusion injury was observed. Ischemia-reperfusion induced the expression of MCP-1 mRNA and protein in injured kidneys, followed by CCR2-positive macrophages in interstitium in wild-type mice. The expression of MCP-1 was decreased in CCR2-deficient mice compared with wild-type mice. The number of interstitial infiltrated macrophages was markedly smaller in the CCR2-deficient mice after ischemia-reperfusion. CCR2-deficient mice decreased the number of interstitial inducible nitric oxide synthase-positive cells after ischemia-reperfusion. The area of tubular necrosis in CCR2-deficient mice was significantly lower than that of wild-type mice after ischemia-reperfusion. In addition, CCR2-deficient mice diminished KC, macrophage inflammatory protein 2, epithelial cell-derived neutrophil-activating peptide 78, and neutrophil-activating peptide 2 expression compared with wild-type mice accompanied with the reduction of interstitial granulocyte infiltration. Similarly, propagermanium and RS-504393 reduced the number of interstitial infiltrated cells and tubular necrosis up to 96 h after ischemia-reperfusion injury. These results revealed that MCP-1 via CCR2 signaling plays a key role in the pathogenesis of renal ischemia-reperfusion injury through infiltration and activation of macrophages, and it offers a therapeutic target for ischemia-reperfusion.
Understanding the Functions of Plant Disease Resistance Proteins (2003)

Many disease resistance (R) proteins of plants detect the presence of disease-causing bacteria, viruses, or fungi by recognizing specific pathogen effector molecules that are produced during the infection process. Effectors are often pathogen proteins that probably evolved to subvert various host processes for promotion of the pathogen life cycle. Five classes of effector-specific R proteins are known, and their sequences suggest roles in both effector recognition and signal transduction. Although some R proteins may act as primary receptors of pathogen effector proteins, most appear to play indirect roles in this process. The functions of various R proteins require phosphorylation, protein degradation, or specific localization within the host cell. Some signaling components are shared by many R gene pathways whereas others appear to be pathway specific. New technologies arising from the genomics and proteomics revolution will greatly expand our ability to investigate the role of R proteins in plant disease resistance.
Genome-wide methylation and expression differences in HPV(+) and HPV(-) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis (2011)

Oncogenic human papillomaviruses (HPV) are associated with nearly all cervical cancers and are increasingly important in the etiology of oropharyngeal tumors. HPV-associated head and neck squamous cell carcinomas (HNSCC) have distinct risk profiles and appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation is widely recognized as a mechanism in the progression of HNSCC, but the extent to which this mechanism is consistent between HPV(+) and HPV(-) tumors is unknown. To investigate the epigenetic regulation of gene expression in HPV-induced and carcinogen-induced cancers, we examined genome-wide DNA methylation and gene expression in HPV(+) and HPV(-) SCC cell lines. We used two platforms: the Illumina Infinium Methylation BeadArray and tiling arrays, and confirmed illustrative examples with pyrosequencing and quantitative PCR. These analyses indicate that HPV(+) cell lines have higher DNA methylation in genic and LINE-1 regions than HPV(-) cell lines. Differentially methylated loci between HPV(+) and HPV(-) cell lines significantly correlated with HPV-typed HNSCC primary tumor DNA methylation levels. Novel findings include higher promoter methylation of polycomb repressive complex 2 target genes in HPV(+) cells compared to HPV(-) cells and increased expression of DNMT3A in HPV(+) cells. Additionally, CDKN2A and KRT8 were identified as interaction hubs among genes with higher methylation and lower expression in HPV(-) cells. Conversely, RUNX2, IRS-1 and CCNA1 were major hubs with higher methylation and lower expression in HPV(+) cells. Distinct HPV(+) and HPV(-) epigenetic profiles should provide clues to novel targets for development of individualized therapeutic strategies.
Dielectric property and conduction mechanism of ultrathin zirconium oxide films (2001)

Stoichiometric, uniform, amorphous ZrO2 films with an equivalent oxide thickness of ∼1.5 nm and a dielectric constant of ∼18 were deposited by an atomic layer controlled deposition process on silicon for potential applications in metal–oxide–semiconductor (MOS) devices. The conduction mechanism is identified as Schottky emission at low electric fields and as Poole–Frenkel emission at high electric fields. The MOS devices showed low leakage current, small hysteresis (&amp;lt;50 mV), and low interface state density (∼2×1011 cm−2 eV−1). Microdiffraction and high-resolution transmission electron microscopy showed a localized monoclinic phase of α-ZrO2 and an amorphous interfacial ZrSixOy layer which has a corresponding dielectric constant of 11.
Determination of Generalized Permeability Function and Field Energy Density in Artificial Magnetics Using the Equivalent-Circuit Method (2007)

The equivalent-circuit model for artificial magnetic materials based on various arrangements of broken loops is generalized by taking into account losses in the substrate or matrix material. It is shown that a modification is needed to the known macroscopic permeability function in order to correctly describe these materials. Depending on the dominating loss mechanism (conductive losses in metal parts or dielectric losses in the substrate), the permeability function has different forms. The proposed circuit model and permeability function are experimentally validated. Furthermore, starting from the generalized circuit model, we derive an explicit expression for the electromagnetic field energy density in artificial magnetic media. This expression is valid at low frequencies and in the vicinity of the resonance also when dispersion and losses in the material are strong. The currently obtained results for the energy density are compared with the results obtained using different methods. As a practical application example, we calculate the quality factor of a microwave resonator made of an artificial magnetic material using the proposed equivalent-circuit method and compare the result with a formula derived for a special case by a different method known from the literature
Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: Evidence suggesting multiple cholesterol esterification enzymes in mammals (1996)

The microsomal enzyme acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) catalyzes the esterification of cellular cholesterol with fatty acids to form cholesterol esters. ACAT activity is found in many tissues, including macrophages, the adrenal glands, and the liver. In macrophages, ACAT is thought to participate in foam cell formation and thereby to contribute to atherosclerotic lesion development. Disruption of the gene for ACAT (Acact) in mice resulted in decreased cholesterol esterification in ACAT-deficient fibroblasts and adrenal membranes, and markedly reduced cholesterol ester levels in adrenal glands and peritoneal macrophages; the latter finding will be useful in testing the role of ACAT and macrophage foam cell formation in atherosclerosis. In contrast, the livers of ACAT-deficient mice contained substantial amounts of cholesterol esters and exhibited no reduction in cholesterol esterification activity. These tissue-specific reductions in cholesterol esterification provide evidence that in mammals this process involves more than one form of esterification enzyme.
Influence of carbon to nitrogen ratios on soybean somatic embryo (cv. Jack) growth and composition (2013)

Soybean [Glycine max (L.) Merr.] seed are valued for their protein and oil content. Soybean somatic embryos cultured in Soybean Histodifferentiation and Maturation (SHaM) medium were examined for their suitability as a model system for developing an understanding of assimilate partitioning and metabolic control points for protein and oil biosynthesis in soybean seed. This report describes the growth dynamics and compositional changes of SHaM embryos in response to change in the carbon to nitrogen ratio of the medium. It was postulated that at media compositions that were sufficient to support maximal growth rates, changes in the C:N ratio are likely to influence the partitioning of resources between the various storage products, especially protein and oil. As postulated, at steady-state growth rates, embryo protein content was strongly correlated with decreasing C:N ratios and increasing glutamine consumption rates. However, oil content remained relatively unchanged across the C:N ratio range tested, and resources were instead directed towards the starch and residual biomass (estimated by mass balance) pools in response to increasing C:N ratios. Protein and oil were inversely related only at concentrations of sucrose in the medium <88 mM, where carbon limited growth and no starch was found to accumulate in the tissues. These observations and the high reproducibility in the data indicate that SHaM embryos are an ideal model system for the application of metabolic flux analysis studies designed to test hypotheses regarding assimilate partitioning in developing soybean seeds.
Isolation and Characterization of an Allergen-Rich Fraction Derived from Cultures of &lt;i&gt;Dermatophagoides pteronyssinus&lt;/i&gt; (1989)

An allergen-rich fraction derived from mature cultures of Dermatophagoides pteronyssinus was isolated. Results of radio-allergosorbent tests and the disclosure of IgE-binding proteins after their electrophoretic transfer from sodium dodecyl sulphate-polyacrylamide gel to nitrocellulose sheets revealed that both important groups of allergens, Der p I and Der p II, seem to be contained in the above-mentioned fraction. Analysis using crossed immuno-electrophoresis (CIE) disclosed 5-7 antigens and a corresponding enzymatic assay for the specificity of patient's IgE in CIE revealed that 4 of the antigens also are allergens. Moreover, an allergen was detected which apparently was not discovered when using CIE. The fraction in question was fractionated further and subsequent analysis by CIE indicated the purification of 1 antigen.
Interleukin-1β and Tumor Necrosis Factor-α Induce Chemokine and Matrix Metalloproteinase Gene Expression in Human Colonic Subepithelial Myofibroblasts (2002)

These observations indicate that chemokine secretion and ECM metabolism are collectively regulated by the proinflammatory cytokines, IL-1beta and TNF-alpha, in colonic subepithelial myofibroblasts. Thus, colonic subepithelial myofibroblasts may play an important role in the pathophysiology of inflammation in the colon.
Adenosine deaminase inhibitors. Synthesis of deaza analogs of erythro-9-(2-hydroxy-3-nonyl) adenine (1984)

Structural analogues of erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), in which the adenine moiety of the molecule was modified, were prepared in order to investigate the structural requirement of EHNA as an inhibitor of adenosine deaminase (ADA). Thus, 1- and 3-deaza-EHNA and their 6-deamino analogues were synthesized and evaluated as inhibitors of ADA from calf intestine. Inhibition studies indicated that isosteric substitution of pyrimidine nitrogens by carbons could be tolerated at the enzymatic binding site. In fact, 3-deaza-EHNA was found to have an inhibitory activity comparable to EHNA itself, and 1-deaza-EHNA, though less potent, is a good inhibitor. The 6-amino group gives an important contribution to the enzymatic binding if the N1 nitrogen is also present, conferring on the compound the characteristic of a semitight inhibitor.
KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia (2017)

Once-daily valbenazine significantly improved tardive dyskinesia in participants with underlying schizophrenia, schizoaffective disorder, or mood disorder. Valbenazine was generally well tolerated, and psychiatric status remained stable. Longer trials are necessary to understand the long-term effects of valbenazine in patients with tardive dyskinesia.
Discovery and Pharmacological Characterization of a Novel Rodent-Active CCR2 Antagonist, INCB3344 (2005)

This report describes the characterization of INCB3344, a novel, potent and selective small molecule antagonist of the mouse CCR2 receptor. The lack of rodent cross-reactivity inherent in the small molecule CCR2 antagonists discovered to date has precluded pharmacological studies of antagonists of this receptor and its therapeutic relevance. In vitro, INCB3344 inhibits the binding of CCL2 to mouse monocytes with nanomolar potency (IC(50) = 10 nM) and displays dose-dependent inhibition of CCL2-mediated functional responses such as ERK phosphorylation and chemotaxis with similar potency. Against a panel of G protein-coupled receptors that includes other CC chemokine receptors, INCB3344 is at least 100-fold selective for CCR2. INCB3344 possesses good oral bioavailability and systemic exposure in rodents that allows in vivo pharmacological studies. INCB3344 treatment results in a dose-dependent inhibition of macrophage influx in a mouse model of delayed-type hypersensitivity. The histopathological analysis of tissues from the delayed-type hypersensitivity model demonstrates that inhibition of CCR2 leads to a substantial reduction in tissue inflammation, suggesting that macrophages play an orchestrating role in immune-based inflammatory reactions. These results led to the investigation of INCB3344 in inflammatory disease models. We demonstrate that therapeutic dosing of INCB3344 significantly reduces disease in mice subjected to experimental autoimmune encephalomyelitis, a model of multiple sclerosis, as well as a rat model of inflammatory arthritis. In summary, we present the first report on the pharmacological characterization of a selective, potent and rodent-active small molecule CCR2 antagonist. These data support targeting this receptor for the treatment of chronic inflammatory diseases.
High-resolution three-dimensional tomographic diffractive microscopy of transparent inorganic and biological samples (2008)

We have developed a tomographic diffractive microscope, equipped with a fluorescence confocal scanner. We measure experimentally the lateral resolution using an edge method and by comparing tomographic images of the same samples with wide-field and laser scanning confocal microscopy images; a scanning electron microscope image serves as a reference. The experimental resolution is shown to be to about 130 nm, or lambda/(3.5 NA). This instrument also permits one to measure 3D, complex index of refraction distributions, a quantity that is not accessible to conventional microscopes, and we show how this feature may be used to observe KCl crystals, absorption of which is very weak.
Deciphering the Cellular Targets of Bioactive Compounds Using a Chloroalkane Capture Tag (2015)

Phenotypic screening of compound libraries is a significant trend in drug discovery, yet success can be hindered by difficulties in identifying the underlying cellular targets. Current approaches rely on tethering bioactive compounds to a capture tag or surface to allow selective enrichment of interacting proteins for subsequent identification by mass spectrometry. Such methods are often constrained by ineffective capture of low affinity and low abundance targets. In addition, these methods are often not compatible with living cells and therefore cannot be used to verify the pharmacological activity of the tethered compounds. We have developed a novel chloroalkane capture tag that minimally affects compound potency in cultured cells, allowing binding interactions with the targets to occur under conditions relevant to the desired cellular phenotype. Subsequent isolation of the interacting targets is achieved through rapid lysis and capture onto immobilized HaloTag protein. Exchanging the chloroalkane tag for a fluorophore, the putative targets identified by mass spectrometry can be verified for direct binding to the compound through resonance energy transfer. Using the interaction between histone deacetylases (HDACs) and the inhibitor, Vorinostat (SAHA), as a model system, we were able to identify and verify all the known HDAC targets of SAHA as well as two previously undescribed targets, ADO and CPPED1. The discovery of ADO as a target may provide mechanistic insight into a reported connection between SAHA and Huntington's disease.
Generic Cell Dysfunction in Neurodegenerative Disorders: Role of Surfaces in Early Protein Misfolding, Aggregation, and Aggregate Cytotoxicity (2007)

Recent knowledge supports the idea that early protein aggregates share basic structural features and are responsible for cytotoxicity underlying neurodegeneration; in most cases, early aggregate cytotoxicity apparently proceeds through similar molecular mechanisms and results in similar biochemical modifications. Data suggest that aggregate cytotoxicity may be considered a generic property of the oligomers preceding fibril appearance. Oligomers can interact with cell membranes, impairing their structural organization and destroying their selective ion permeability, eventually culminating with cell death. This process can be influenced by the physicochemical features and aggregation state of amyloids as well as by the physical and biochemical features of cell surfaces. The roles of synthetic and biological surfaces in affecting protein folding and misfolding, in speeding up aggregate nucleation, and as targets of aggregate toxicity is gaining consideration. Recent research has highlighted the involvement of surfaces as protein-misfolding chaperones and aggregation catalysts and their effects in these phenomena.
Disentangling Factors of Variation via Generative Entangling (2012)

Here we propose a novel model family with the objective of learning to disentangle the factors of variation in data. Our approach is based on the spike-and-slab restricted Boltzmann machine which we generalize to include higher-order interactions among multiple latent variables. Seen from a generative perspective, the multiplicative interactions emulates the entangling of factors of variation. Inference in the model can be seen as disentangling these generative factors. Unlike previous attempts at disentangling latent factors, the proposed model is trained using no supervised information regarding the latent factors. We apply our model to the task of facial expression classification.