gebhart/patrepeval huggingface dataset:
Folate Targeting Enables Durable and Specific Antitumor Responses from a Therapeutically Null Tubulysin B Analogue (2008)

The membrane-bound high-affinity folate receptor (FR) is highly expressed on a wide range of primary and metastatic human cancers, such as those originating in ovary, lung, breast, endometrium, kidney, and brain. Because folate-linked conjugates bind to and become internalized within FR-expressing cells (similar to that of free folic acid), we explored the possibility of using the folate ligand to target a potent, semisynthetic analogue of the microtubule inhibitor tubulysin B to FR-enriched tumors. When tested in vitro, a novel folate conjugate, herein referred to as EC0305, was found to specifically inhibit the growth of a panel of FR-positive cell lines (IC50 range, 1-10 nmol/L) in a dose-dependent manner, whereas cells lacking FR expression were unaffected. The potency of EC0305 was also confirmed against a human KB xenograft-nu/nu mouse cancer model. Here, a brief three times per week, 2-week regimen yielded remarkable antitumor activity (100% tumor-free animals) without causing significant weight loss or major organ tissue degeneration. In contrast, antitumor activity was completely abolished in EC0305-treated animals that were co-dosed with an excess of a nontoxic folate-containing analogue, thereby confirming that the antitumor effect of this agent was mediated by FRs. The advantage provided by folate conjugation was further proved by the untargeted free drug, which was found to be completely inactive at both tolerable and highly toxic dose levels. Collectively, these results show that this potent antiproliferative tubulysin compound can be specifically delivered to FR-positive tumors to provide substantial therapeutic benefit using well-tolerable dosing regimens.
Kinetic study of iridium(I) complexes as homogeneous hydrogenation catalysts (1968)

A study is described of the kinetics of reactions in which the complexes trans-IrX(CO)(PPh 3 ) 2 , where X = Cl, Br, and I, are used for the catalytic homogeneous hydrogenation of olefinic bonds. Catalytic activity is enhanced in coordinating solvents such as dimethylacetamide. The rate law is complex, showing between zero and first order in each of iridium, substrate, and hydrogen concentrations, and the mechanisms proposed show the importance of a dissociation step in making available a coordination site on the transition metal complex. The dependence of rate on the halogen followed the order I &gt; Br &gt; Cl. Quite remarkably, traces of oxygen in the system enhance the hydrogenation rate considerably.
The rates of G:C-->T:A and G:C-->C:G transversions at CpG dinucleotides in the human factor IX gene. (1994)

We have identified eight independent transversions at CpG in 290 consecutive families with hemophilia B. These eight transversions account for 16.3% of all independent transversions in our sample, yet the expected frequency of CpG transversions at random in the factor IX gene is only 2.6% (P < .01). The aggregate data suggest that the two types of CpG transversions (G:C-->T:A and G:C-->C:G) possess similar mutation rates (24.8 x 10(-10) and 20.6 x 10(-10), respectively), which are about fivefold greater than the comparable rates for transversions at non-CpG dinucleotides. The enhancement of transversions at CpG suggests that the model by which mutations occur at CpG may need to be reevaluated. The relationship, if any, between deamination of 5-methyl cytosine and enhancement of transversions at CpG remains to be defined.
Adenovirus-Mediated p21 (WAF1/SDII/CIP1) Gene Transfer Induces Apoptosis of Human Cervical Cancer Cell Lines (1999)

p21((WAF1/SDII/CIP1)) (p21) arrests cell growth by inhibiting cyclin-depend kinases. To explore the potential of using p21 for the gene therapy of cervical cancer, we infected human papillomavirus (HPV)-positive cervical cancer cells (HeLa, SiHa, and Z172) and HPV-negative cervical cancer cells (C33A) with recombinant adenovirus encoding p21 cDNA. The results revealed that effective inhibition of cell growth could be achieved by sense p21 adenovirus but not antisense p21 adenovirus infection and occurred through apoptosis as measured by DNA fragmentation and chromatin condensation. Apoptosis was also observed in xenografts of human cervical cancer cells infected with sense p21 adenovirus, as confirmed by in situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). The apoptosis was not prevented by overexpression of the bcl-2 transgene. To sum up, the apoptotic effect suggests that p21 should be a tumoricidal agent instead of a tumoristatic agent in preventing cervical cancers. In addition, our report substantiates the combination of the high efficiency of adenovirus vector-mediated gene delivery and the apoptotic effect of p21.
Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery (2003)

Although we acknowledge the limitations of a nonblinded interventional trial, stress doses of hydrocortisone seem to attenuate systemic inflammation in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass and improve early outcome.
Specificity study to evaluate induction of aberrant crypts in murine colons. (1988)

We have previously reported on our findings of aberrant crypts (AC) in the colons of rodents treated with a colon carcinogen. In this report, the specificity of AC formation was assessed by testing a variety of agents for their ability to induce AC in the colons of CF1 and C57BL/6J mice. In addition, the ability of each of the agents to induce nuclear aberrations (NA) was assessed and compared with the AC data. The test agents included hydrazines, polycyclic aromatic hydrocarbons, aromatic amines, and nitrosocompounds. The colons were assessed for AC 2 or 4 weeks following a single treatment with the test agent. Of the seven agents that induced AC formation, five were colon carcinogens and the other two were agents believed to be carcinogenic to organs other than the colon. None of the five agents believed to be noncarcinogens induced AC whereas three of them did induce NA in at least one of the strains of mice tested. Comparison of AC and NA induction for each test agent showed that all agents that induced AC also induced NA and that the converse was not true. The findings of the present study indicate that AC are induced specifically in response to colon carcinogens and support our contention that AC are preneoplastic lesions.
Peripherally η1-Platinated Organometallic Porphyrins as Building Blocks for Multiporphyrin Arrays (2003)

The modification of peripherally metalated meso-η1-platiniometalloporphyrins, such as trans-[PtBr(NiDAPP)(PPh3)2] (H2DAPP = 5-phenyl-10,20-bis(3‘,5‘-di-tert-butylphenyl)porphyrin), leads to the analogous platinum(II) nitrato and triflato electrophiles in almost quantitative yields. Self-assembly reactions of these meso-platinioporphyrin tectons with pyridine, 4,4‘-bipyridine, or various meso-4-pyridylporphyrins in chloroform generate new multicomponent organometallic porphyrin arrays containing up to five porphyrin units. These new types of supramolecular arrays are formed exclusively in high yields and are stable in solution or in the solid state for extended periods. They were characterized by multinuclear NMR and UV−visible spectroscopy as well as high-resolution electrospray ionization mass spectrometry.
Transcription profiles of LPS-stimulated THP-1 monocytes and macrophages: a tool to study inflammation modulating effects of food-derived compounds (2010)

An assay was developed to study inflammation-related immune responses of food compounds on monocytes and macrophages derived from THP-1 cell line. First strategy focused on the effects after stimulation with either lipopolysaccharide (LPS) or Concanavalin A (ConA). Gene expression kinetics of inflammation-related cytokines (IL-1β, IL-6, IL-8, IL-10 and TNF-α), inflammation-related enzymes (iNOS and COX-2), and transcription factors (NF-κB, AP-1 and SP-1) were analyzed using RT-PCR. Time dependent cytokine secretion was investigated to study the inflammation-related responses at protein level. LPS stimulation induced inflammation-related cytokine, COX-2 and NF-κB genes of THP-1 monocytes and THP-1 macrophages with the maximum up-regulation at 3 and 6 h, respectively. These time points, were subsequently selected to investigate inflammation modulating activity of three well known immuno-modulating food-derived compounds; quercetin, citrus pectin and barley glucan. Co-stimulation of LPS with either quercetin, citrus pectin, or barley glucan in THP-1 monocytes and macrophages showed different immuno-modulatory activity of these compounds. Therefore, we propose that simultaneously exposing THP-1 cells to LPS and food compounds, combined with gene expression response analysis are a promising in vitro screening tool to select, in a limited time frame, food compounds for inflammation modulating effects.
Cross‐linking of ubiquitin, HSP27, parkin and α‐synuclein by γ‐glutamyl‐ε‐lysine bonds in Alzheimer's neurofibrillary tangles (2004)

The accumulation of misfolded proteins in intracellular inclusions is a generic feature of neurodegenerative disorders. Although heavily ubiquitylated, the aggregated proteins are not degraded by the proteasomes. A possible reason for this phenomenon may be a modification of deposited proteins by transglutaminases forming gamma-glutamyl-epsilon-lysine (GGEL) cross-links between distinct proteins. Here, we show that the frequency of GGEL cross-links is an order of magnitude higher in Alzheimer's brain cortex than in age-matched or younger controls. This difference is due to the accumulation of GGEL cross-links in ubiquitin-immunopositive protein particles present in both Alzheimer's brains and those from aged individuals. The highly cross-linked protein aggregates show immunoreactivity to antibodies against tau and neurofilament proteins, and partially also to alpha-synuclein, indicating that these structures are inherent in Alzheimer's neurofibrillary tangles and Lewy bodies. Using mass sequence analysis, we identified the same six pairs of peptide sequences cross-linked in both senile and Alzheimer's specimens: Gln31 and Gln190 of HSP27 protein are cross-linked with Lys29 and Lys48 of ubiquitin and HSP27 therefore may cross-link two (poly)ubiquitin chains. One lysine residue of parkin and one of alpha-synuclein were also found to be cross-linked. The data suggest that cross-linking of (poly)ubiquitin moieties via HSP27 may have a role in the stabilization of the intraneuronal protein aggregates by interference with the proteasomal elimination of unfolded proteins.
Translation of the Alzheimer Amyloid Precursor Protein mRNA Is Up-regulated by Interleukin-1 through 5′-Untranslated Region Sequences (1999)

The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD.
주조 A356.0 AL-SIC 복합재료의 기계적 성질과 파괴과정에 대한 공정 SI 입자의 영향 (2017)

In this study an attempt has been made to improve mechanical properties of a cast aluminum matrix composite. Detailed microstructural analyses of a cast A356.0 Al-SiC composite indicated that SiC particulates and eutectic Si particles were segregated to the intercellular regions. The presence of these eutectic Si particles resulted in cleavage fracture along the intercellular regions, which deteriorated mechanical properties of the cast composite. In-situ SEM fracture observations clearly showed that eutectic Si particles were cracked first before the matrix-SiC decohesion or the SiC breakage occurred. In order to modify the distribution of eutectic Si particles the cast composite was re-cast with adding small amount of Sr. Tensile properties of the re-cast composite with 0.03wt.% Sr were significantly improved. The improvement of mechanical properties is attributed to a more homogeneous distribution of SiC and eutectic Si particles due to the addition of Sr and recasting.
Characterization of a temperature-sensitive influenza B virus mutant defective in neuraminidase (1993)

ts5, a temperature-sensitive mutant of influenza B virus, belongs to one of seven recombination groups. When the mutant infected MDCK cells at the nonpermissive temperature (37.5 degrees C), infectious virus was produced at very low levels compared with the yield at the permissive temperature (32 degrees C) and hemagglutinating and enzymatic activities were undetectable. However, viral protein synthesis and transport of hemagglutinin (HA) and neuraminidase (NA) to the cell surface were not affected. The NA was found as a monomer within cells even at 32 degrees C, in contrast to wild-type virus NA, existing mostly as an oligomer, but the mutant had oligomeric NA, like the wild-type virus. Its enzymatic activity was more thermolabile than that of wild-type virus. Despite the low yield, large aggregates of progeny virus particles were found to accumulate on the cell surface at the nonpermissive temperature, and these aggregates were broken by treatment with bacterial neuraminidase, with the concomitant appearance of hemagglutinating activity, suggesting that NA prevents the aggregation of progeny virus by removal of neuraminic acid from HA and cell receptor, allowing its release from the cells. Further treatment with trypsin resulted in the recovery of infectivity. When bacterial NA was added to the culture early in infection, many hemagglutinable infectious virus was produced. We also suggest that the removal of neuraminic acid from HA by NA is essential for the subsequent cleavage of HA by cellular protease. Nucleotide sequence analysis of RNA segment 6 revealed that ts5 encoded five amino acid changes in the NA molecule but not in NB.
Production and characterization of a polyclonal antibody to the c‐erb B‐3 protein: Examination of c ‐erb B‐3 protein expression in adenocarcinomas (1992)

A polyclonal rabbit antibody was raised to the c-erbB-3 protein using a synthetic peptide corresponding to amino acids 1229-1241 of the predicted protein sequence of c-erbB-3. In Western blot analysis this antibody detects a single band at approximately 165 kD in a c-erbB-3 transfected (293/HER-3) human cell line. c-erbB-3 protein expression was then examined in a variety of adenocarcinomas. Expression of c-erbB-3 protein was indicated by membrane and/or cytoplasmic tumour cell immunoreactivity in formalin-fixed, paraffin-embedded tissue sections. c-erbB-3 protein was detected in a series of 13 out of 14 primary breast carcinomas, 3 of 5 gastric adenocarcinomas, 8 of 9 colonic adenocarcinomas, 2 of 9 prostatic adenocarcinomas, 0 of 6 renal cell carcinomas, 1 of 4 primary lung adenocarcinomas, and 5 of 7 endometrial adenocarcinomas. Immunohistochemical expression of the c-erbB-3 protein appears to be a relatively common event in adenocarcinomas, and further studies are now warranted to establish the role of the c-erbB-3 protein in neoplasia.
Recursive region segmentation by analysis of histograms (2005)

Recursive segmentation of an image into regions using histograms is one of the most widely used techniques for image segmentation. At CMU, several versions of a region segmentation program have been developed based on this technique (Ohlander, Price, Shafer and Kanade). Based on these experiences, this paper discusses issues of recursive region segmentation in the context of PHOENIX, the newest version of region segmentation program, running on a VAX 11/780 under UNIX. The issues discussed in this paper include: Image features to be used in histogramming; comparison of the algorithm with other techniques; important improvements made in PHOENIX over its predecessor (Ohlander and Price); and some inherent problems in histogram-based segmentation together with suggestions for minimizing them. PHOENIX is being incorporated into the ARPA Image Understanding Testbed, under construction at SRI International.
Functional analysis of ssaJ and the ssaK/U operon, 13 genes encoding components of the type III secretion apparatus of Salmonella Pathogenicity Island 2 (1997)

We have investigated the structure and transcriptional organization of 13 genes of Salmonella Pathogenicity Island 2 (SPI2) that encode components of the second type III secretion apparatus of Salmonella typhimurium. ssaK, L, M, V, N, O, P, Q, R, S, T, U constitute one operon of 10 kb. ssaJ lles upstream of ssaK and is the terminal gene of another operon. The deduced products of ssaJ, ssaK, ssaV, ssaN, ssaO, ssaQ, ssaR, ssaS, ssaT, and ssaU show greatest similarity to the Yersinia spp. genes yscJ, yscL, lcrD, yscN, yscO, yscQ, yscR, yscS, yscT, and yscU, respectively. The products of the ssaL, ssaM and ssaP genes do not have significant similarity to products of other type III secretion systems, and might be important for the specific function of the SPI2 type III secretion system. Bacterial strains carrying different ssa mutations display minor alterations in terms of serum sensitivity when compared with the wild-type strain, but none are defective in replication within macrophage-like RAW 264.7 cells. However, some of the ssa mutant strains invade HEp2 cells less efficiently and are less cytotoxic to RAW 264.7 macrophages than the wild-type strain. We show that the invasion defect is correlated with a lack of SipC in culture supernatants of these mutant strains. SipC is a product of the SPI1 type III secretion system of S. typhimurium, and is important for epithelial cell invasion. Therefore, mutations in SPI2 can affect the SPI1 secretion system, which raises the possibility of an interaction between the two type III secretion systems.
750 MHz 1H and 1H-13C NMR Spectroscopy of Human Blood Plasma (1995)

High-resolution 750 MHz 1H NMR spectra of control human blood plasma have been measured and assigned by the concerted use of a range of spin-echo, two-dimensional J-resolved, and homonuclear and heteronuclear (1H-13C) correlation methods. The increased spectral dispersion and sensitivity at 750 MHz enable the assignment of numerous 1H and 13C resonances from many molecular species that cannot be detected at lower frequencies. This work presents the most comprehensive assignment of the 1H NMR spectra of blood plasma yet achieved and includes the assignment of signals from 43 low M(r) metabolites, including many with complex or strongly coupled spin systems. New assignments are also provided from the 1H and 13C NMR signals from several important macromolecular species in whole blood plasma, i.e., very-low-density, low-density, and high-density lipoproteins, albumin, and alpha 1-acid glycoprotein. The temperature dependence of the one-dimensional and spin-echo 750 MHz 1H NMR spectra of plasma was investigated over the range 292-310 K. The 1H NMR signals from the fatty acyl side chains of the lipoproteins increased substantially with temperature (hence also molecular mobility), with a disproportionate increase from lipids in low-density lipoprotein. Two-dimensional 1H-13C heteronuclear multiple quantum coherence spectroscopy at 292 and 310 K allowed both the direct detection of cholesterol and choline species bound in high-density lipoprotein and the assignment of their signals and confirmed the assignment of most of the lipoprotein resonances.
Application of infrared microspectroscopy and chemometric analysis for screening the acrylamide content in potato chips (2013)

Currently, LC-MS/MS and GC-MS are the most common techniques used for acrylamide analysis in foods. However, these techniques require extensive sample preparation, highly specialized machinery, and are time consuming. Our objective was to evaluate the feasibility of using attenuated total reflectance (ATR) mid-infrared microspectroscopy (IRMS) as a rapid method for detection and quantification of acrylamide in potato chips. The acrylamide content of 58 commercially available potato chips (110–1876 μg kg−1) was determined by LC-MS/MS. Spectra for aqueous extracts of potato chips with and without solid phase extraction (SPE) clean-up were collected using ATR-IRMS. Partial Least Squares Regression (PLSR) was applied to generate calibration models to predict acrylamide levels. Samples were grouped into three categories: regular potato chips (n = 46), potato chips with seasonings (n = 12) and combination of regular and seasoned potato chips (n = 58). Overall, a good linear correlation was found between the predicted acrylamide levels of independent sample sets and actual measured acrylamide concentrations by LC-MS/MS (rPred was between 0.91 and 0.92). Standard error of prediction (SEP) for the models ranged between 22.1 and 28.9 μg L−1. Models developed without SPE cleaning provided similar or better results than those with SPE treatment, which makes IRMS technology even more promising for acrylamide analysis since the SPE step can be avoided. Our results indicate that IRMS can be used as a simple, rapid and high-throughput screening tool for acrylamide detection and quantification in potato chips and help addressing risk management, assessing safety and brand equity.
Tumor Hypoxia: Causative Factors, Compensatory Mechanisms, and Cellular Response (2004)

Hypoxia is a characteristic feature of locally advanced solid tumors resulting from an imbalance between oxygen (O(2)) supply and consumption. Major causative factors of tumor hypoxia are abnormal structure and function of the microvessels supplying the tumor, increased diffusion distances between the nutritive blood vessels and the tumor cells, and reduced O(2) transport capacity of the blood due to the presence of disease- or treatment-related anemia. Tumor hypoxia is a therapeutic concern since it can reduce the effectiveness of radiotherapy, some O(2)-dependent cytotoxic agents, and photodynamic therapy. Tumor hypoxia can also negatively impact therapeutic outcome by inducing changes in the proteome and genome of neoplastic cells that further survival and malignant progression by enabling the cells to overcome nutritive deprivation or to escape their hostile environment. The selection and clonal expansion of these favorably altered cells further aggravate tumor hypoxia and support a vicious circle of increasing hypoxia and malignant progression while concurrently promoting the development of more treatment-resistant disease. This pattern of malignant progression, coupled with the demonstration of a relationship between falling hemoglobin level and worsening tumor oxygenation, highlights the need for effective treatment of anemia as one approach for correcting anemic hypoxia in tumors, and in so doing, possibly improving therapeutic response.