gebhart/patrepeval huggingface dataset:
The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy (2012)

DNA damaging agents such as radiotherapy and gemcitabine are frequently used for the treatment of pancreatic cancer. However, these treatments typically provide only modest benefit. Improving the low survival rate for pancreatic cancer patients therefore remains a major challenge in oncology. Inhibition of the key DNA damage response kinase ATR has been suggested as an attractive approach for sensitization of tumor cells to DNA damaging agents, but specific ATR inhibitors have remained elusive. Here we investigated the sensitization potential of the first highly selective and potent ATR inhibitor, VE-821, in vitro. VE-821 inhibited radiation- and gemcitabine-induced phosphorylation of Chk1, confirming inhibition of ATR signaling. Consistently, VE-821 significantly enhanced the sensitivity of PSN-1, MiaPaCa-2 and primary PancM pancreatic cancer cells to radiation and gemcitabine under both normoxic and hypoxic conditions. ATR inhibition by VE-821 led to inhibition of radiation-induced G 2/M arrest in cancer cells. Reduced cancer cell radiosurvival following treatment with VE-821 was also accompanied by increased DNA damage and inhibition of homologous recombination repair, as evidenced by persistence of γH2AX and 53BP1 foci and inhibition of Rad51 foci, respectively. These findings support ATR inhibition as a novel approach to improve the efficacy and therapeutic index of standard cancer treatments across a large proportion of pancreatic cancer patients.
Endoplasmic Reticulum Stress-induced mRNA Splicing Permits Synthesis of Transcription Factor Hac1p/Ern4p That Activates the Unfolded Protein Response (1997)

An intracellular signaling from the endoplasmic reticulum (ER) to the nucleus, called the unfolded protein response (UPR), is activated when unfolded proteins are accumulated in the ER under a variety of stress conditions ("ER stress"). We and others recently identified Hac1p/Ern4p as a transcription factor responsible for the UPR in Saccharomyces cerevisiae. It was further reported that Hac1p (238 aa) is detected only in ER-stressed cells, and its expression is mediated by unconventional splicing of HAC1 precursor mRNA. The splicing replaces the C-terminal portion of Hac1p; it was proposed that precursor mRNA is also translated but the putative product of 230 aa is rapidly degraded by the ubiquitin-proteasome pathway. We have identified and characterized the same regulated splicing and confirmed its essential features. Contrary to the above proposal, however, we find that the 238-aa product of mature mRNA and the 230-aa-type protein tested are highly unstable with little of no difference in stability. Furthermore, we demonstrate that the absence of Hac1p in unstressed cells is due to the lack of translation of precursor mRNA. We conclude that Hac1p is synthesized as the result of ER stress-induced mRNA splicing, leading to activation of the UPR.
Factors for Promoting Polyhydroxyalkanoate (PHA) Synthesis in Bio-Nutrient-Removal and Recovery System (2018)

In the near future, the bio-nutrient-removal (BNR) system is no longer confined to meet the nitrogen and phosphorus removal requirement, but operated for sequestering and recovering carbon, nitrogen and phosphorus from wastewaters and generate more high-value-added by-products. Polyhydroxyalkanoate (PHA) is a metabolite of microorganisms under unfavourable growth conditions for their own energy storage and utilization. More and more researches have gradually uncovered the impacting factors on the microbial synthesis of PHA in the BNR and none-BNR system. This mini-review summarizes the impacting factors of carbon source types and dosage, nitrogen concentration and phosphorus recovery and temperature variation on the enrichment of PHA by microbial populations. Furthermore, the potential genomic reasons for promoting PHA synthesis are introduced. It provides a new perspective to stimulate the PHA synthesis by the functional microorganisms and its potential benefit for bio-nutrients removal and recovery in BNR system.
IL‐13 regulates cancer invasion and metastasis through IL‐13Rα2 via ERK/AP‐1 pathway in mouse model of human ovarian cancer (2011)

Previously, we have demonstrated that a variety of human cancers including the ovarian cancer express IL-13Rα2, a high affinity receptor for IL-13. Herein, we have examined if IL-13 regulates invasion and metastasis of ovarian cancer through IL-13Rα2 in vitro and in vivo in animal models of human ovarian cancer. We tested cell invasion and protease activity in IL-13Rα2-overexpressing and IL-13Rα2-negative ovarian tumor cell lines. IL-13 treatment significantly augmented both cell invasion and enzyme activities in only IL-13Rα2-positive cells but not in IL-13Rα2-negative cells in vitro. Mechanistically, IL-13 enhanced ERK1/2, AP-1 and MMP activities only in IL-13Rα2-positive cells but not in IL-13Rα2-negative cells. In contrast, other signaling pathways such as IRS1/2, PI3K and AKT do not seem to be involved in IL-13 induced signaling in ovarian cancer cell lines. Highly specific inhibitors for MMP and AP-1 efficiently inhibited both invasion and protease activities without impacting the basal level invasion and protease activities in vitro. In orthotopic animal model of human ovarian cancer, IL-13Rα2-positive tumors metastasized to lymph nodes and peritoneum earlier than IL-13Rα2-negative tumors. Interestingly, the IL-13Rα2-positive tumor bearing mice died earlier than mice with IL-13Rα2-negative tumor. Intraperitoneal injection of IL-13 further shortened survival of IL-13Rα2-positive tumor bearing mice compared to IL-13Rα2-negative tumor mice. IL-13Rα2-positive tumors and lymph node metastasis expressed higher levels of MMPs and higher ERK1/2 activation compared to IL-13Rα2-negative tumors. Taken together, IL-13Rα2 is involved in cancer metastasis through activation of ERK/AP-1 and that targeting IL-13Rα2 might not only directly kill primary tumors but also prevent cancer metastasis.
Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). (1986)

ICAM-1 is a cell surface glycoprotein originally defined by a monoclonal antibody (MAb) that inhibits phorbol ester-stimulated leukocyte aggregation. Staining of frozen sections and immunofluorescence flow cytometry showed intercellular adhesion molecule-1 (ICAM-1) is expressed on non-hematopoietic cells such as vascular endothelial cells, thymic epithelial cells, certain other epithelial cells, and fibroblasts, and on hematopoietic cells such as tissue macrophages, mitogen-stimulated T lymphocyte blasts, and germinal center dendritic cells in tonsils, lymph nodes, and Peyer's patches. ICAM-1 staining on vascular endothelial cells is most intense in T cell areas in lymph nodes and tonsils showing reactive hyperplasia. ICAM-1 is expressed in low amounts on peripheral blood leukocytes. Phorbol ester-stimulated differentiation of myelomonocytic cell lines greatly increases ICAM-1 expression. ICAM-1 expression on dermal fibroblasts is increased threefold to fivefold by either interleukin 1 (IL 1) or interferon-gamma at 10 U/ml over a period of 4 or 10 hr, respectively. The induction is dependent on protein and mRNA synthesis and is reversible. ICAM-1 displays Mr heterogeneity in different cell types with a Mr of 97,000 on fibroblasts, 114,000 on the myelomonocytic cell line U937, and 90,000 on the B lymphoblastoid cell JY. ICAM-1 biosynthesis involves a Mr approximately 73,000 intracellular precursor. The non-N-glycosylated form resulting from tunicamycin treatment has a Mr of 55,000. ICAM-1 isolated from phorbol myristic acetate (PMA) stimulated U937 and from fibroblasts yields an identical major product of Mr = 60,000 after chemical deglycosylation. ICAM-1 MAb interferes with the adhesion of phytohemagglutinin blasts, and the adhesion of the cell line SKW3 to human dermal fibroblast cell layers. Pretreatment of fibroblasts but not lymphocytes with ICAM-1 MAb, and of lymphocytes but not fibroblasts with lymphocyte function-associated antigen 1 MAb inhibits adhesion. Intercellular adhesion is increased by prior exposure of fibroblasts to IL 1, and correlates with induction of ICAM-1.
Functional Characterization of the Brain-specific FGF-1 Promoter, FGF-1.B (1995)

Expression of alternatively spliced human FGF-1 (or aFGF) transcripts is regulated in a tissue-specific manner via multiple promoters. To identify the cis-regulatory elements in the brain-specific FGF-1.B promoter, we constructed a series of promoter deletions fused to the luciferase reporter gene and transfected into an FGF-1.B positive glioblastoma cell line, U1240MG, and a 1.B negative cell line, U1242MG. Results of transient transfections indicate three elements that are involved in the positive regulation of FGF-1.B expression. The core promoter is located in a 40-base pair region (between -92 and -49), and two regulatory regions (RR-1 and RR-2) are located within the 540-base pair region 5' to the major transcription start site (defined as +1). Electrophoretic mobility shift assays and footprinting analysis have identified sequence-specific binding sites in RR-1 and RR-2. Mutants of RR-2 abolished binding to nuclear proteins and showed diminished luciferase reporter activity. The effects seen are specific for the U1240MG cell line, supporting a role for RR-2 in the tissue-specific regulation of FGF-1.B. Southwestern analysis using an oligonucleotide probe derived from RR-2 (nucleotides -489 to -467) further identified a 37-kDa protein that is present in nuclear extracts from U1240MG and brain but not from U1242MG.
Purification and spectral study of a microbial fatty acyltransferase: activation by limited proteolysis (1990)

A fatty acyltransferase with a reaction mechanism similar to that of mammalian lecithin: cholesterol acyltransferase has been purified from culture supernatants of a mutant Aeromonas salmonicida containing the cloned Aeromonas hydrophila structural gene. Typically, more than 35 mg of protein were isolated from 2 L of culture supernatant. The amino-terminal sequence, amino acid composition, and molecular weight of the purified protein corresponded to predictions based on the sequence of the gene, indicating that the signal sequence had been correctly removed during export but that no further processing had occurred. Analysis of the far-UV circular dichroic (CD) spectrum of the enzyme showed that it consists of 31% alpha-helix, 21% beta-sheet, and 16% beta-turn, with 12% of aperiodic form. Treatment of the purified protein with a variety of proteases resulted in nicking near the C-terminus. This led to an increase in enzyme activity against lipids in erythrocyte membranes and increased rate of hydrolysis of p-nitrophenyl butyrate. Activation was accompanied by a change in the CD spectrum and a change in its aggregation state. The trypsin cut site was located between the two cysteines in the enzyme. Evidence is presented that the cysteines are joined by a disulfide bond and therefore cannot participate in acyl transfer. This may distinguish the microbial enzyme from lecithin:cholesterol acyltransferase. This is the second extracellular A. hydrophila protein that we have shown can be activated by proteolysis after it is released.
Biosynthetic origin of conjugated double bonds: Production of fatty acid components of high-value drying oils in transgenic soybean embryos (1999)

Vegetable oils that contain fatty acids with conjugated double bonds, such as tung oil, are valuable drying agents in paints, varnishes, and inks. Although several reaction mechanisms have been proposed, little is known of the biosynthetic origin of conjugated double bonds in plant fatty acids. An expressed sequence tag (EST) approach was undertaken to characterize the enzymatic basis for the formation of the conjugated double bonds of alpha-eleostearic (18:3Delta(9cis, 11trans,13trans)) and alpha-parinaric (18:4Delta(9cis,11trans, 13trans,15cis)) acids. Approximately 3,000 ESTs were generated from cDNA libraries prepared from developing seeds of Momordica charantia and Impatiens balsamina, tissues that accumulate large amounts of alpha-eleostearic and alpha-parinaric acids, respectively. From ESTs of both species, a class of cDNAs encoding a diverged form of the Delta(12)-oleic acid desaturase was identified. Expression of full-length cDNAs for the Momordica (MomoFadX) and Impatiens (ImpFadX) enzymes in somatic soybean embryos resulted in the accumulation of alpha-eleostearic and alpha-parinaric acids, neither of which is present in untransformed soybean embryos. alpha-Eleostearic and alpha-parinaric acids together accounted for as much as 17% (wt/wt) of the total fatty acids of embryos expressing MomoFadX. These results demonstrate the ability to produce fatty acid components of high-value drying oils in transgenic plants. These findings also demonstrate a previously uncharacterized activity for Delta(12)-oleic acid desaturase-type enzymes that we have termed "conjugase."
Circulating cell-free DNA in serum as a biomarker of colorectal cancer (2013)

Aims The aim of this study was to report circulating cell-free DNA using ALU247 and ALU247/ALU115 biomarkers in serum of operated and non-operated patients with colorectal cancer (CRC). Methods To undertake this, 90 blood samples were collected, including 30 samples from healthy volunteers; 27 samples from CRC non-operated patients and 33 samples from CRC-operated patients. Circulating cell-free DNA was verified through quantitative real-time PCR (qPCR) using ALU115 and ALU247 primers. Results With regard to the ALU115-qPCR biomarker, the increased levels of circulating cell-free DNA in serum of non-operated patients were significant when compared with control (p&lt;0.05). Moreover, levels of ALU247-qPCR biomarker were statistically significant between non-operated versus operated and non-operated versus control groups (p=0.000). With regard to the ALU247/115-qPCR biomarker, significant differences were observed between control versus non-operated patients (p=0.019), operated versus non-operated patients (p=0.005) and control versus operated patients (p=0.043). Conclusions Thus, the ALU247 and ALU247/ALU115-qPCR biomarkers may be important in detecting and monitoring CRC patients in both early and late stages.
Frequency of bowel movements and the future risk of Parkinson’s disease (2001)

Findings indicate that infrequent bowel movements are associated with an elevated risk of future PD. Further study is needed to determine whether constipation is part of early PD processes or is a marker of susceptibility or environmental factors that may cause PD.
Joint Power-Distortion Optimization on Devices with MPEG-4 AVC/H.264 Codec (2006)

Energy supply is always a bottleneck in wireless video applications. To prolong the battery life, a typical wireless video encoding and streaming system should have the capability of dynamically adjusting its encoding parameters based on the remaining battery supply. In this paper, we consider two types of application scenarios as well as the associated optimization problems. The first one is, given a video quality level, how to find out the optimized encoding parameters so that the total power consumption is minimized. The second one is, given a fixed power consumption level, how to calculate the optimized encoding parameters so that the video quality is best. Accordingly, we jointly consider the power consumption and video quality and pose the above two problems into a uniform optimization framework. Under this framework, we give an efficient solution for the MPEG-4 AVC/H.264 codec and Wi-Fi transmission devices based on a detailed complexity analysis of the H.264 encoder. The analysis method can be easily extended to other video encoder and transmission configuration.
Cheddar cheesemaking with recombinant calf chymosin synthesized in Escherichia coli (1985)

SUMMARY The cheesemaking properties of recombinant chymosin from Escherichia coli were compared with those of standard rennet in parallel trials with three single strain starters. For each pair of cheeses the cheesemaking characteristics, recoveries of milk solids in the curds and compositions were similar. The rates and types of proteolysis and texture development during ripening between cheeses made with the two coagulants were not significantly different.
The Wlds mutation delays robust loss of motor and sensory axons in a genetic model for myelin-related axonopathy. (2003)

Mice deficient in the peripheral myelin component P0 mimic severe forms of inherited peripheral neuropathies in humans, with defective myelin formation and consequent axonal loss. We cross-bred these mice with the spontaneous mutant C57BL/Wld(s) typically showing protection from Wallerian degeneration because of fusion of the ubiquitination factor E4B (Ube4b) and nicotinamide mononucleotide adenylyltransferase (Nmnat) genes. We found that in the double mutants, the robust myelin-related axonal loss is reduced at 6 weeks and 3 months of age. Moreover, retrograde labeling from plantar nerves revealed an increased survival of motor axons. These motor axons appeared functionally active because both the amplitude of compound muscle action potentials and muscle strength were less reduced in the double mutants. At 6 months of age, reduction of axonal loss was no longer detectable in the double mutants when compared with littermates carrying the P0 null mutation only, although the Wld(s) gene was not reduced in its expression at this age. We conclude that myelin-related axonal loss is a process having some features in common with Wallerian degeneration. Introducing the Wld(s) gene would be a promising approach to delaying detrimental axonal loss in myelin disorders.
Improvement of metabolic control and changes of fatty acid composition do not alter platelet aggregability and thromboxane production in type 2 diabetes mellitus. (1992)

To evaluate whether improvement of metabolic control or changes in fatty acid composition of serum lipids may alter thromboxane (TXB2) formation and platelet function we followed up 25 newly diagnosed type 2 diabetics without angiopathy for about 6 months. Improvement of metabolic control was associated with significant decrease in total cholesterol (C), HDL-C, LDL-C, triglycerides (TG) and ratios of total C/HDL-C and LDL-C/HDL-C, respectively. Palmitic acid of TG and phospholipids decreased significantly whereas linoleic acid increased in the two serum lipids. The ADP-induced platelet aggregability and sensitivity were not altered. There was even no effect on TXB2 synthesis capacity of clotting whole blood during 6 months of treatment. Platelet aggregability and TXB2 formation were not correlated to the degree of metabolic control, nor was there any correlation to serum lipids and their fatty acid composition.
On linear parasitic array of dipoles with reactive loading (1973)

Center loaded linear parasitic arrays of dipoles are examined. It is shown that capacitive loading increases the phase velocity of the slow wave on the structure while inductive loading reduces it. For the infinite array, used as a transmission line, this has the effect of modifying the cutoff frequency and the bandwidth. This is experimentally verified for the capacitive loading. For a simple finite array without a reflector, due to end effects only a small bandwidth widening is observed. However, when the finite array is attached with a suitable reflector, a significant widening of bandwidth is observed. In both these cases the loading causes a significant shifting of the center operating frequency. This effect is utilized to build a tunable Yagi array with varactor loading. With variable bias this loading can effectively be adjusted to double the operational bandwidth. Also it is shown that it is possible to sustain the optimum array directivity over a very wide bandwidth without bias adjustments, by a special loading network.
BALB/c.CBA/N mice carrying the defective Btkxid gene are resistant to pristane-induced plasmacytomagenesis (1999)

The X-chromosome from the CBA/N mouse which carries the defective Bruton's tyrosine kinase (Btk) allele (Xxid) has been introgressively backcrossed onto the plasmacytoma (PCT) induction-susceptible BALB/cAN. Inbred BALB/c.CBA/N-xid/xid (C.CBA/N) mice raised and maintained in our conventional colony were given three 0.5 ml injections of pristane and were highly refractory to PCT induction. Only one PCT was found among 59 mice followed for > or =300 days. Twenty mice were examined at day 200 for foci of plasma cells in the oil granuloma. Ten mice had small foci of plasma cells, most of which were plasmacytotic, embedded in the inflammatory oil granuloma. In one there were multiple foci, but most of the mice had only one or two foci. F1 hybrid XxidY males derived from CBA/N females crossed to BALB/cAnPt were also resistant to PCT induction, while heterozygous and homozygous XY males were susceptible. C.CBA/N mice can develop extensive mucosal plasma cells as well as plasma cell accumulations in oil granuloma tissue, but the precursors of these plasma cells do not give rise to PCT in genetically susceptible hosts. The failure of C.CBA/N mice to develop PCT is probably due to the elimination of B cell clones that can be perpetuated by repeated exposure to thymus-independent type 2 antigens.
Poly(p-phenylene vinylene) in light-emitting diodes: Nature of the lowest singlet and triplet excited states and effects of derivatization (1995)

Poly(p-phenylene vinylene), PPV, has attracted a tremendous interest in the past few years, especially in the field of optic and electro-optic devices such as light-emitting diodes (LED`s). Here we focus our attention on three issues of prime importance when studying PPV (or its oligomers) as an emitting layer. The first topic deals with the modelling of the nature of the lowest singlet excited state (from which fluorescence originates) and of the lowest triplet excited states (also reached by the system following recombination of the charge carriers). In a second part, we analyze the way the optical transitions are affected by derivatization; we modulate the locations of the frontier levels by fixing {pi}-donor (methoxy) and {pi}-acceptor (cyano) substituents along the conjugated backbone. Finally, we investigate the metallization of the cyano-PPVs, by aluminum or alkali metals.
Which Cyclin E Prevails as Prognostic Marker for Breast Cancer? Results from a Retrospective Study Involving 635 Lymph Node–Negative Breast Cancer Patients (2006)

Our study shows that both CCNE1 and CCNE2 qualify as independent prognostic markers for lymph node-negative breast cancer patients, and that CCNE1 may provide additional information for specific subgroups of patients.
Epidermal Growth Factor Enhances Striatal Dopaminergic Parameters in the 1‐Methyl‐4‐Phenyl‐l, 2, 3, 6‐Tetrahydropyridine‐Treated Mouse (1991)

Intracerebroventricular infusion of epidermal growth factor (EGF) into mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of dopaminergic nigrostriatal neurons partially enhanced the content of dopamine (DA) and 3,4-dihydroxyphenylacetic acid as well as the activity of tyrosine hydroxylase in the striatum. EGF also enhanced these parameters in control, unlesioned animals. Neurotrophic activity also was observed in embryonic mesencephalic cultures, where EGF enhanced DA uptake after a lesion with the neurotoxic metabolite of MPTP, 1-methyl-4-phenylpyridinium ion. Our in vivo and in vitro studies suggest that EGF may be a neurotrophic factor for dopaminergic neurons, or may act indirectly by inducing the release of a dopaminergic trophic factor from other cells.