gebhart/patrepeval huggingface dataset:
The combi-targeting concept: a new cell signaling-based model for the selective targeting of the epidermal growth factor receptor (EGFR)- and Her2-expressing solid tumor cells by the complex combi-molecule RB24 (NSC 741279) (2007)

4175 Within the context of the “Combi-Targeting” concept, we designed RB24 to inhibit EGFR or Her2 phosphorylation and to further degrade upon hydrolysis to RB10 (another EGFR/Her2 inhibitor) + a DNA methylating species. In vitro analyses using fluorescence microscopy, comet and Annexin-V binding assays showed that RB24 released RB10 in the perinuclear region, damaged DNA and induced apoptosis in the human MDA-MB-435 breast cancer cells. Transfection of the latter cells with ErbB1 or ErbB2 correlated with 2-3 fold higher levels of DNA damage, enhanced cell death by apoptosis and increased intensity of fluorescence associated with RB10 in the perinuclear region. The selective enhancement of DNA lesions in the transfected cells was abolished by co-incubation with exogenous RB10, suggesting that intact RB24 bound to its cognate perinuclear sites prior to releasing the alkylating species. Analysis of key signaling proteins in the cells demonstrated a DNA-damage dependent activation of JNK and down-regulation of Bad through inhibition of EGFR or Her2 phosphorylation by RB24. This translated in to a 10-20-fold stronger cytocidal activity by RB24 when compared with its clinical counterpart Temodal®.The results suggest a targeting model based on a by-stander effect that increases the levels of DNA damage in the transfectants and a cooperative enhancement of apoptosis through JNK activation and down regulation of Bad. This convergent mechanism may account for the remarkable potency of RB24 against the oncogenic expressing transfectants. The results in toto indicate that the Combi-Targeting concept may well represent a novel strategy to enhance the potency of alkylators in EGFR- and Her2-expressing cells.
Structure of benzoylferrocene (1988)

(C 5 H 5 ) Fe (C 5 H 4 COC 6 H 5 ) cristallise dans P2 1/n avec affinement jusqu'a 0,028. Le groupement carbonyl fait un angle de 14,2 o avec le plan contenant le groupement cyclopentadiene. Le groupement phenyl fait un angle de 26,2 o avec le plan contenant le groupement carbonyl
Unstable and stable CAD gene amplification: importance of flanking sequences and nuclear environment in gene amplification. (1987)

We analyzed the amplification of the CAD gene in independently isolated N-(phosphonacetyl)-L-aspartate-resistant clones derived from single parental clones in two mouse cell lines. We report for the first time that the CAD gene is amplified unstably in mouse cells, that the degree of instability varies greatly between clones, and that minute chromosomes and highly unstable chromosomelike structures contain the amplified sequences. These data are most consistent with the idea that the amplified unit in each clone consists of different flanking DNA and that such differences engender amplified sequences with unequal stability. We also introduced the mouse chromosome containing the CAD gene into hamster cells by microcell-mediated chromosome transfer to determine whether the propensity for unstable extrachromosomal amplification of the mouse CAD gene would prevail in the hamster cell nuclear environment. We report that the mouse CAD gene was amplified stably in expanded chromosomal regions in each of seven hybrids that were analyzed. This observation is consistent with the idea that the nuclear environment influences whether mutants containing intra- or extrachromosomally amplified sequences will be isolated.
Local neurogenic regulation of rat hindlimb circulation: CO2‐induced release of calcitonin gene‐related peptide from sensory nerves (1997)

1. The mechanism of release of calcitonin gene-related peptide (CGRP) from sensory nerves in response to skeletal muscle contraction was investigated in the rat hindlimb in vivo and in vitro. 2. In the anaesthetized rat, sciatic nerve stimulation at 10 Hz for 1 min caused a hyperaemic response in the hindlimb. During the response, partial pressure of CO2 in the venous blood effluent from the hindlimb significantly increased from 43 +/- 3 to 73 +/- 8 mmHg, whereas a small decrease in pH and no appreciable change in partial pressure of O2 were observed. 3. An intra-arterial bolus injection of NaHCO3 (titrated to pH 7.2 with HCl), which elevated PCO2 of the venous blood, caused a sustained increase in regional blood flow of the iliac artery. Capsaicin (0.33 micromol kg(-1), i.a.) and a specific calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP(8-37), (100 nmol kg(-1) min(-1), i.v.) significantly suppressed the hyperaemic response to NaHCO3. Neither ND(omega)-nitro-L-arginine methyl ester (1 micromol kg(-1) min(-1), i.v.) nor indomethacin (5 mg kg(-1), i.v.) affected the response. 4. The serum level of CGRP-like immunoreactivity in the venous blood was significantly increased by a bolus injection of NaHCO3 (pH = 7.2) from 50 +/- 4 to 196 +/- 16 fmol ml(-1). 5. In the isolated hindlimb perfused with Krebs-Ringer solution, a bolus injection of NaHCO3 (pH = 7.2) caused a decrease in perfusion pressure which was composed of two responses, i.e., an initial transient response and a slowly-developing long-lasting one. CGRP(8-37) significantly inhibited the latter response by 73%. 6. These results suggest that CO2 liberated from exercising skeletal muscle activates capsaicin-sensitive perivascular sensory nerves locally, which results in the release of CGRP from their peripheral endings, and then the released peptide causes local vasodilatation.
Seasonal Distribution Of Cold Weather Injuries In The U.s. Army (2018)

The incidence of and risk factors for cold weather injury (CWI) in the US Army have been well characterized. Unlike the ‘heat season,’ when the risk of heat illness is highest and application of risk mitigation procedures is mandatory, there is no definition of the ‘cold season’ and the proportion of CWI that occur outside of a defined cold season is unknown. PURPOSE: To identify the cold season and to determine the within-year seasonal distribution of CWI at select Army installations. METHODS: The 10 US Army installations with the highest frequency of CWI from 1 July 2008-30 June 2013 were identified and used for analysis. In- and out-patient CWI data (ICD-9-CM codes 991.0-991.9, first, second or third diagnoses only) were obtained from the Defense Medical Surveillance System. Piecewise regression analysis was utilized to determine the critical cut points at which trends in CWI significantly increased or decreased, indicating the start and end, respectively, of the cold season. The proportional distribution of EHI within the cold season, overall and by installation, was determined. RESULTS: During the study period there were 1,012 CWI and the overall rate was 0.79 per 10,000 person-months. The highest rate occurred during the month of February (2.16 per 10,000 person-months) and the installation with the highest rate was Ft Drum, NY (5.40 per 10,000 person-months). There was at least one CWI during every week of the year during the 5 year study period. Piecewise regression analyses indicated that on average the cold season started during week 14 (Sept 30) and ended during week 39 (March 24). Using this definition, 83.2% (842/2012) of CWI occurred during the cold season. The longest cold season occurred at Ft Wainwright, AK (34 weeks) and the shortest at Ft Carson, CO (17 weeks), illustrating the considerable variability between locations. CONCLUSIONS: Our data suggest that the risk of CWI exists year round at select Army installations, though further research sub-grouped by type of CWI is warranted. Based on the piecewise regression analysis, we recommend that the ‘cold season’ starts 1 October and continues through March, as ~83% of CWI occurred during this period.
Fast Luminescence in Silicon-Germanium Nanostructures (2013)

Epitaxially-grown three-dimensional Si/SiGe nanostructures produce photoluminescence and electroluminescence in the desired spectral range of 1.3-1.6 μm. We show that by controlling and modifying such Ge-rich SiGe nanoclusters during growth it is possible to fabricate very fast and hence more efficient SiGe light-emitting devices. The physics of carrier recombination in these Si/SiGe nanostructures is discussed. The present results provide another possible route toward CMOS compatible light emitters.
Lifetime prediction of IGBT modules based on linear damage accumulation (2017)

In this paper, the lifetime prediction of power device modules based on the linear damage accumulation in conjunction with real mission profile assessment is studied. Four tests are performed under two superimposed power cycling conditions using an advanced power cycling test setup with 600 V, 30 A, 3-phase molded IGBT modules. The superimposed power cycling conditions are made based on a new lifetime model in respect to junction temperature swing duration, which has been developed based on 39 power cycling test results. The experimental results validate the lifetime prediction of the IGBT modules based on the linear damage accumulation by comparing it with the predicted lifetime from the lifetime model.
Active site imprinting on Ti oxocluster metal-organic framework for the photocatalytic hydrogen release from formic acid (2022)

On-board hydrogen release from liquid organic carriers is a process that can make feasible the use of H2 as transportation fuel. Formic acid is considered as one of the most convenient liquid hydrogen organic carriers, since it can be easily obtained from CO2, it is water soluble and it makes unnecessary to recover the H2-depleted byproducts. Compared to the more conventional thermal catalytic decomposition of formic acid, the use of light in combination with a photocatalyst has been much less explored. Herein, we report a new paradigm in MOF photocatalysis that is the use of a microporous titanium oxocluster based metal-organic framework (Ti-MOF) endowed by formate-imprinted active sites, namely MIP-177_LT (MIP stands for Materials from Institute of Porous Materials of Paris, LT for Low Temperature), as a highly efficient photocatalyst for H2 release from formic acid without the need to neutralize acidity or the use sacrificial agents or noble metals. Noteworthy, a quantum efficiency of 22 % has been determined for the photocatalytic H2 release that is highly remarkable for a non-toxic noble metal-free photocatalyst.
A pressure-balanced electrostatically-actuated microvalve (1990)

A new microvalve structure designed to enhance the limited actuation forces available in microfabricated devices by using a pressure-balancing scheme is reported. The concept is to allow the fluid to provide a balancing force on the moving part of the device, thereby reducing the force required to open the valve. Various methods can be used to actuate the valve, but electrostatic actuation is chosen since it is readily integrated with the valve fabrication sequence. The process for implementing the valve concept uses multiple wafer bonding steps (three in the present prototype) and has yielded valves which have been successfully actuated in air using voltages below 350 V.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Construction of a 2,6-Difunctionalized 2-Methyl-2H-1-benzopyran Library by Using a Solid-Phase Synthesis Protocol (2005)

[reaction: see text] A library containing 1200 analogues of 2,6-difunctionalized 2-methyl-2H-1-benzopyran was constructed by using a solid-phase synthesis protocol. Polymer-bound 6-amido-, 6-sulfonamido-, and 6-uredo-functionalized 2-hydroxymethyl-2-methylbenzopyrans 10 were prepared as part of a first-generation diversification step by employing reactions of respective acid halides, sulfonyl chlorides, and isocyanates with the amine precursor 7. Transformations of the resin-bound intermediates 10 by reactions with alkyl and acid halides were then used to produce a diverse series of 2,6-difunctionalized 2-methyl-2H-1-benzopyran analogues 12 and 14.
Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita (2011)

Dyskeratosis congenita (DC) is a genetic disorder of defective tissue maintenance and cancer predisposition caused by short telomeres and impaired stem cell function. Telomerase mutations are thought to precipitate DC by reducing either the catalytic activity or the overall levels of the telomerase complex. However, the underlying genetic mutations and the mechanisms of telomere shortening remain unknown for as many as 50% of DC patients, who lack mutations in genes controlling telomere homeostasis. Here, we show that disruption of telomerase trafficking accounts for unknown cases of DC. We identify DC patients with missense mutations in TCAB1, a telomerase holoenzyme protein that facilitates trafficking of telomerase to Cajal bodies. Compound heterozygous mutations in TCAB1 disrupt telomerase localization to Cajal bodies, resulting in misdirection of telomerase RNA to nucleoli, which prevents telomerase from elongating telomeres. Our findings establish telomerase mislocalization as a novel cause of DC, and suggest that telomerase trafficking defects may contribute more broadly to the pathogenesis of telomere-related disease.
Genus Salsola: Chemistry, Biological Activities and Future Prospective—A Review (2022)

The genus <i>Salsola</i> L. (Russian thistle, Saltwort) includes halophyte plants and is considered one of the largest genera in the family Amaranthaceae. The genus involves annual semi-dwarf to dwarf shrubs and woody tree. The genus <i>Salsola</i> is frequently overlooked, and few people are aware of its significance. The majority of studies focus on pollen morphology and species identification. <i>Salsola</i> has had little research on its phytochemical makeup or biological effects. Therefore, we present this review to cover all aspects of genus <i>Salsola,</i> including taxonomy, distribution, differences in the chemical constituents and representative examples of isolated compounds produced by various species of genus <i>Salsola</i> and in relation to their several reported biological activities for use in folk medicine worldwide.
Enhancing the CO2 Adsorption Capacity of γ-Al2O3 Supported Alkali and Alkaline-Earth Metals: Impacts of Dual Function Material (DFM) Preparation Methods (2022)

The term “dual function material” (DFM) was coined by our research group for codispersed catalysts (e.g., Ru) and alkaline sorbents on the same high-surface-area carrier. These materials allow for combined CO2 capture and catalytic conversion, thus their dual functional nature. Herein, we report an additional, unexpected function; combining Ru with specific adsorbents and carriers substantially enhances CO2 capture capacity. Investigation of several Ru + sorbent/carrier formulations shows that the enhancement effect is not inherent with Ru but requires a specific combination of DFM components. Most surprisingly, significant enhancement of CO2 adsorption is retained during multiple cycles of adsorption in O2 and methanation, where RuOx species are present. Ru0 is known to adsorb CO2, as required for methanation, but the significant enhancement in the presence of RuOx indicates that Ru does not directly contribute to the adsorption mechanism. Instead, Ru allows for more efficient activation of adsorption sites on the alkaline sorbent via catalytic reduction during pretreatment. This is verified by greater adsorption capacity in materials with higher catalytic activity. These findings open up new pathways for designing materials with higher capture capacity than conventionally thought. Such materials can play a key role in mitigating the negative effects of climate change.
METHYLTRANSFERASE SMYD5 EXAGGERATES INFLAMMATORY BOWEL DISEASE BY REGULATING PPAR-γ COACTIVATOR 1-α STABILITY (2021)

Abstract Background and Aims The expression and role of methyltransferase SET and MYND domain-containing protein 5 (SMYD5) in inflammatory bowel diseases (IBD) is completely unknown. Here, we investigated the role and the underlying mechanism of epithelial SMYD5 in IBD pathogenesis and progression. Methods The expression and subcellular localization of SMYD5 and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) were examined by Western blot analysis, immunofluorescence staining, and immunohistochemistry in intestinal epithelial cells (IECs) and in colon tissues from human IBD patients and mice with experimental colitis. Mice with Smyd5 conditional knockout in IECs and littermate controls were subjected to DSS-induced experimental colitis and the disease severity and inflammation were assessed. SMYD5-regulated mitochondrial biogenesis was examined by RT-qPCR and transmission electron microscopy and mitochondrial oxygen consumption rate was measured in a Seahorse Analyzer system. The interaction between SMYD5 and PGC-1α was determined by co-immunoprecipitation assay. PGC-1α degradation and turnover (half-life) were analyzed by cycloheximide chase assay. SMYD5-mediated PGC-1α methylation was measured via in vitro methylation followed by mass spectrometry to identify the specific lysine residues that were methylated. Results Up-regulated SMYD5 and down-regulated PGC-1α were observed in IECs from IBD patients and mice with experimental colitis. However, Smyd5 depletion in IECs protected mice from DSS-induced colitis. SMYD5 was critically involved in regulating mitochondrial biology such as mitochondrial biogenesis, respiration, and apoptosis. Mechanistically, SMYD5 regulated mitochondrial functions in a PGC-1α dependent manner. Further, SMYD5 mediated lysine methylation of PGC-1α and facilitated its ubiquitination and proteasomal degradation. Conclusion SMYD5 attenuates mitochondrial functions in IECs and promotes IBD progression by enhancing the proteasome-mediated degradation of PGC-1α protein in a methylation-dependent manner. Strategies to decrease SMYD5 expression and/or increase PGC-1α expression in IECs might be a promising therapeutic approach to treat patients with IBD.
Possible role of endorphins in schizophrenia and other psychiatric disorders (1979)

The impressive mood-manipulating effects of opiates, as well as the psychotomimetic properties of some opiate antagonists have long been familiar to pharmacologists. When the brain endorphins were discovered (Terenius and Wahlström, 1975a; Pasternak et al., 1975; Hughes, 1975; Cox et al., 1975) it soon became evident that the activity state of the newly postulated peptidergic neuronal system (Elde et al., 1976) might help to elucidate some psychiatric diseases, which had hitherto only been clinically defined. After Terenius and Wahlström (1975b) had developed a technique for the semiquantitative measurement of two major endorphin fractions (I and II) in cerebrospinal fluid (CSF), this method was applied in various psychiatric disorders (Terenius et al., 1976; Landström et al., 1977). Preliminary reports have shown that before treatment some cases of schizophrenia had supranormal CSF levels of fraction I and the same was true of certain phases of manic-depressive psychosis. Another approach to these problems consisted intrials of an opiate antagonist in schizophrenia. In a pilot study schizophrenic hallucinations were found to be temporarily reversed by administration of naloxone (Gunne etal., 1977). The present chapter reports an extension of these studies.
Structure and bonding in photodiffused amorphous Ag-GeSe2thin films (1988)

Grazing-incidence x-ray scattering (GIXS) techniques have been used to study the local and intermediate-range order in photodiffused amorphous Ag-${\mathrm{GeSe}}_{2}$ thin films and a variety of Ag-Ge-Se alloys. Using synchrotron-radiation sources, the GIXS technique can be used in conjunction with radial-distribution-function analysis, differential anomalous x-ray scattering, and differential distribution-function analysis to study the structure of very thin amorphous films. With these techniques, we have determined that the local atomic structure of Ag-${\mathrm{GeSe}}_{2}$ films satisfies a model where Se-Ag dative bonds are formed, one Se-Ag covalent bond is formed for each Ag atom added (below a critical composition), and Ge-Ge bonds are created as Ag is added. This last result significantly modifies the intermediate-range order in this system.
The Effect of Selected Factors on Polyphenol Content and Antioxidant Activity in Potato Tubers (2006)

The total polyphenol (TP) content in and antioxidant activity of potato tubers of four yellow-fleshed varieties and two purple-fleshed varieties from the 2004 harvest were assayed. The TP content was determined with the Folin-Ciocalteau reagent and antioxidant antiradical activity by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. Significant differences in the TP content between the groups of yellow-fleshed varieties were found. Significant differences between yellow and purple-fleshed potatoes were also found in antioxidant activity both between yellow and purple-fleshed varieties and within purple-fleshed varieties. The higher potatoes-growing regions showed an apparent tendency to higher TP contents in analyzed varieties. In some varieties the effect of four variants of growing was assayed and a significant effect of high potassium doses (200 and 130 kg K2O per hectare) on the decrease in TP was estimated.
The Absolute Stereostructure of Panaxytriol,a Biologically Active Diacetylenic Acetogenin, from Ginseng Radix Rubra. (1995)

The absolute stereostructure of panaxytriol (1), a diacetylenic constituent of Ginseng Radix Rubra, was determined by applying the modified Mosher method and the CD exciton chirality method to be expressed as (3R, 9R, 10R)-heptadec-1-ene-4, 6-diyne-3, 9, 10-triol.
Modified mask methods for pattern accuracy enhancement in electron beam lithography (1996)

In projection-type lithography, delineated resist patterns differ from original mask shapes. In this article, aperture modification methods are investigated to enhance the pattern accuracy of electron beam cell projection lithography. The modified aperture is easily fabricated by decreasing the mask thickness. Although electrons penetrate the mask, enough high scattering contrast can be obtained. In dot delineation, star-shape apertures make better square dots near the resolution limit. In line-and-space delineation, dividing the pattern into small patterns of lower resolution reduces the electron current. This decreases Coulomb effects. In addition, Monte Carlo simulation results also confirm these results. As a result, these methods are expected to be important in the application of projection-type charged particle lithography.
The history of radar in atmospheric investigations (2016)

The groundwork describing the atmospheric environment and the types of flows that radar can study in the Earth's atmosphere has been laid in the previous chapter. We now turn to a brief history of how radars came to be involved with studies of this type.