bluuebunny/crossref_metadata_2025_split huggingface dataset:
ISG20L1 is a p53 family target gene that modulates genotoxic stress-induced autophagy
Authors: Eby Kathryn G. , Rosenbluth Jennifer M. , Mays Deborah J. , Marshall Clayton B. , Barton Christopher E. , Sinha Seema , Johnson Kimberly N. , Tang Luojia , Pietenpol Jennifer A. 
Published: April 2010

Abstract

Background
Autophagy is characterized by the sequestration of cytoplasm and organelles into multimembrane vesicles and subsequent degradation by the cell's lysosomal system. It is linked to many physiological functions in human cells including stress response, protein degradation, organelle turnover, caspase-independent cell death and tumor suppression. Malignant transformation is frequently associated with deregulation of autophagy and several tumor suppressors can modulate autophagic processes. The tumor suppressor p53 can induce autophagy after metabolic or genotoxic stress through transcriptionally-dependent and -independent mechanisms. In this study we expand on the former mechanism by functionally characterizing a p53 family target gene, ISG20L1 under conditions of genotoxic stress.

Results
We identified a p53 target gene, ISG20L1, and show that transcription of the gene can be regulated by all three p53 family members (p53, p63, and p73). We generated an antibody to ISG20L1 and found that it localizes to the nucleolar and perinucleolar regions of the nucleus and its protein levels increase in a p53- and p73-dependent manner after various forms of genotoxic stress. When ectopically expressed in epithelial cancer-derived cell lines, ISG20L1 expression decreased clonogenic survival without a concomitant elevation in apoptosis and this effect was partially rescued in cells that were ATG5 deficient. Knockdown of ISG20L1 did not alter 5-FU induced apoptosis as assessed by PARP and caspase-3 cleavage, sub-G1 content, and DNA laddering. Thus, we investigated the role of ISG20L1 in autophagy, a process commonly associated with type II cell death, and found that ISG20L1 knockdown decreased levels of autophagic vacuoles and LC3-II after genotoxic stress as assessed by electron microscopy, biochemical, and immunohistochemical measurements of LC3-II.

Conclusions
Our identification of ISG20L1 as a p53 family target and discovery that modulation of this target can regulate autophagic processes further strengthens the connection between p53 signaling and autophagy. Given the keen interest in targeting autophagy as an anticancer therapeutic approach in tumor cells that are defective in apoptosis, investigation of genes and signaling pathways involved in cell death associated with autophagy is critical.
Three agonist antibodies in combination with high-dose IL-2 eradicate orthotopic kidney cancer in mice
Authors: Westwood Jennifer A , Darcy Phillip K , Guru Preethi Mayura , Sharkey Janelle , Pegram Hollie J , Amos Sally M , Smyth Mark J , Kershaw Michael H 
Published: April 2010

AbstractBackgroundCombination immunotherapies can be effective against subcutaneous tumors in mice but the effect against orthotopic malignant disease is less well characterized. In particular, a combination of three agonist antibodies, termed Tri-mAb, consisting of anti-DR5, anti-CD40 and anti-CD137 has previously been demonstrated to eradicate a large proportion of subcutaneous renal cell carcinoma (Renca) tumors (75% long-term survival), but the effect against orthotopic disease is not known.PurposeTo determine the relative response of orthotopic tumors, we inoculated Renca into the kidney followed by treatment with Tri-mAb.ResultsWe found that orthotopic tumors responded much less to treatment (~13% survival), but a significant improvement in survival was achieved through the addition of IL-2 to the treatment regimen (55% survival). All three agonist antibodies and high dose IL-2, 100,000 IU for up to six doses, were required. CD8+T cells were also required for optimal anti-tumor responses. Coadministration of IL-2 led to enhanced T cell activity as demonstrated by an increased frequency of IFN-gamma-producing T cells in tumor-draining lymph nodes, which may have contributed to the observed improvement of therapy against kidney tumors.ImplicationsResponses of subcutaneous tumors to immunotherapy do not necessarily reflect how orthotopic tumors respond. The use of combination immunotherapy stimulating multiple facets of immunity and including cytokine support for T cells can induce effective anti-tumor responses against orthotopic and metastatic tumors.
Transcriptional regulation of matrix metalloproteinase-1 and collagen 1A2 explains the anti-fibrotic effect exerted by proteasome inhibition in human dermal fibroblasts
Authors: Goffin Laurence , Seguin-Estévez Queralt , Alvarez Montserrat , Reith Walter , Chizzolini Carlo 
Published: April 2010

Abstract
Introduction
Extracellular matrix (ECM) turnover is controlled by the synthetic rate of matrix proteins, including type I collagen, and their enzymatic degradation by matrix metalloproteinases (MMPs). Fibrosis is characterized by an unbalanced accumulation of ECM leading to organ dysfunction as observed in systemic sclerosis. We previously reported that proteasome inhibition (PI) in vitro decreases type I collagen and enhances MMP-1 production by human fibroblasts, thus favoring an antifibrotic fibroblast phenotype. These effects were dominant over the pro-fibrotic phenotype induced by transforming growth factor (TGF)-β. Here we investigate the molecular events responsible for the anti-fibrotic phenotype induced in fibroblasts by the proteasome inhibitor bortezomib.

Methods
The steady-state mRNA levels of COL1A1, COL1A2, TIMP-1, MMP-1, and MMP-2 were assessed by quantitative PCR in human dermal fibroblasts cultured in the presence of TGF-β, bortezomib, or both. Transient fibroblast transfection was performed with wild-type and mutated COL1A1 and MMP-1 promoters. Chromatin immunoprecipitation, electrophoretic mobility shift assay (EMSA), and DNA pull-down assays were used to assess the binding of c-Jun, SP1, AP2, and Smad2 transcription factors. Immunoblotting and immunofluorescent microscopy were performed for identifying phosphorylated transcription factors and their cellular localization.

Results
Bortezomib decreased the steady-state mRNA levels of COL1A1 and COL1A2, and abrogated SP1 binding to the promoter of COL1A2 in both untreated and TGF-β-activated fibroblasts. Reduced COL1A2 expression was not due to altered TGF-β-induced Smad2 phosphorylation, nuclear translocation, or binding to the COL1A2 promoter. In contrast to collagen, bortezomib specifically increased the steady-state mRNA levels of MMP-1 and enhanced the binding of c-Jun to the promoter of MMP-1. Furthermore, disruption of the proximal AP-1-binding site in the promoter of MMP-1 severely impaired MMP-1 transcription in response to bortezomib.

Conclusions
By altering the binding of at least two transcription factors, c-Jun and SP1, proteasome inhibition results in increased production of MMP-1 and decreased synthesis of type I collagen in human dermal fibroblasts. Thus, the antifibrotic phenotype observed in fibroblasts submitted to proteasome inhibition results from profound modifications in the binding of key transcription factors. This provides a novel rationale for assessing the potential of drugs targeting the proteasome for their anti-fibrotic properties.
Early fiberoptic bronchoscopy during non-invasive ventilation in patients with decompensated chronic obstructive pulmonary disease due to community-acquired-pneumonia
Authors: Scala Raffaele , Naldi Mario , Maccari Uberto 
Published: April 2010

Abstract
Introduction
Inefficient clearance of copious respiratory secretion is a cause of non-invasive positive pressure ventilation (NPPV) failure, especially in chronic respiratory patients with community-acquired-pneumonia (CAP) and impaired consciousness. We postulated that in such a clinical scenario, when intubation and conventional mechanical ventilation (CMV) are strongly recommended, the suction of secretions with fiberoptic bronchoscopy (FBO) may increase the chance of NPPV success. The objective of this pilot study was, firstly, to verify the safety and effectiveness of early FBO during NPPV and, secondly, to compare the hospital outcomes of this strategy versus a CMV-based strategy in patients with decompensated chronic obstructive pulmonary disease (COPD) due to CAP who are not appropriate candidates for NPPV because of inefficient mucous clearance and hypercapnic encephalopathy (HE).

Methods
This is a 12-month prospective matched case-control study performed in one respiratory semi-intensive care unit (RSICU) with expertise in NPPV and in one intensive care unit (ICU). Fifteen acutely decompensated COPD patients with copious secretion retention and HE due to CAP undergoing NPPV in RSICU, and 15 controls (matched for arterial blood gases, acute physiology and chronic health evaluation score III, Kelly-Matthay scale, pneumonia extension and severity) receiving CMV in the ICU were studied.

Results
Two hours of NPPV significantly improved arterial blood gases, Kelly and cough efficiency scores without FBO-related complications. NPPV avoided intubation in 12/15 patients (80%). Improvement in arterial blood gases was similar in the two groups, except for a greater PaO2/fraction of inspired oxygen ratio with CMV. The rates of overall and septic complications, and of tracheostomy were lower in the NPPV group (20%, 20%, and 0%) versus the CMV group (80%, 60%, and 40%; P < 0.05). Hospital mortality, duration of hospitalisation and duration of ventilation were similar in the two groups.

Conclusions
In patients with decompensated COPD due to CAP who are candidates for CMV because of HE and inability to clear copious secretions, NPPV with early therapeutic FBO performed by an experienced team is a feasible, safe and effective alternative strategy.
Editorial: CSF1R, CSF-1, and IL-34, a “ménage à trois” conserved across vertebrates
Authors: Droin Nathalie , Solary Eric 
Published: April 2010

Abstract
Editorial discusses the perspectives opened by the recently discovered IL-34, its conservation across species in the biology of the cytokine CSF-1, and identification of a new CSF-1R ligand that could together account for the well-known heterogeneity of monocytes.
Numerical simulation of combustion-driven oil transport on the top land of an internal combustion engine piston
Authors: McGrogan S , Tian T 
Published: April 2010

A mathematical model of a lubricant film attached to the top land of an internal combustion engine piston was formulated. Multidimensional oil transport induced by gas flows within the top land crevice was included in the model, with the intention of predicting the effects of such gas flows on top land carbon deposits. A finite-volume, shock-capturing simulation of the film's free surface was created, and its accuracy verified. Preliminary results were generated using crevice gas flow data taken from a separate computational fluid dynamics (CFD) simulation of a modern diesel engine's combustion process. It was found that combustion-driven gas flows within the top land crevice can have a profound effect on the top land oil film thickness distribution. A fundamental lubricant transport mechanism arising from an interaction between the effects of the engine's reciprocating inertia and those of the gas flow-induced shear forces was discovered. For the engine studied in the present work, the mechanism severely reduced the amount of lubricant in some regions of the top land. An engine designe's clever usage of this mechanism could potentially reduce both oil consumption and top land carbon deposits.
Excavatoids G–K, New 8,17-Epoxybriaranes from the Cultured Octocoral Briareum excavatum (Briareidae)
Authors: Sung Ping-Jyun , Chen Bo-Yuan , Chiang Michael Y , Hou Chi-Hung , Su Yin-Di , Hwang Tsong-Long , Chen Yung-Husan , Chen Jih-Jung 
Published: April 2010

Abstract
Chemical investigations on the cultured octocoral Briareum excavatum have led to the isolation of five new 8,17-epoxybriarane diterpenoids, excavatoids G–K (1–5). The structures of briaranes 1–5 were determined on the basis of spectroscopic methods and the structure of 1 was further confirmed by a single-crystal X-ray diffraction analysis. Cytotoxicity of these metabolites toward various tumor cell lines is described. Excavatoid I (3) was found to show mild inhibitory effects on elastase release and superoxide anion generation by human neutrophils.
Incorporation of Fluorescent-Labeled Non-α-Amino Carboxylic Acids into the N-Terminus of Proteins in Response to Amber Initiation Codon
Authors: Miura Masanori , Muranaka Norihito , Abe Ryoji , Hohsaka Takahiro 
Published: April 2010

Abstract
Incorporation of non-natural amino acid derivatives containing fluorescent groups into proteins is a useful method for protein analyses. Here, we investigated the incorporation of fluorescent-labeled non-α-amino carboxylic acids into the N-terminus of proteins in response to the UAG initiation codon. A series of TAMRA-labeled amino carboxylic acids were synthesized and attached to an amber suppressor initiator tRNA derived from Escherichia coli initiator tRNA. Fluorescent-labeled amino carboxylic acids were successfully incorporated into the N-terminus of streptavidin by adding TAMRA-acylated initiator tRNAs to an E. coli cell-free translation system, although the incorporation efficiency differed depending on the amino carboxylic acid chain length. Based on this observation, 3-aminopropionic acid derivatives labeled with BODIPY, rhodamine, and cyanine fluorophores were designed and synthesized. The fluorescent-labeled 3-aminopropionic acid derivatives developed using BODIPY and rhodamine dyes could be incorporated with good efficiency. On the other hand, 6-aminohexanoic acid was effectively incorporated when labeled with cyanine dyes. The present study demonstrates that translation initiation can accept a wide variety of non-natural substrates and provides a useful method for N-terminal-specific labeling of proteins with various fluorophores.
Photochemical Removal of Benzene Using 172 nm Xe2 Excimer Lamp in N2/O2 Mixtures at Atmospheric Pressure
Authors: Tsuji Masaharu , Kawahara Takashi , Kamo Naohiro , Miyano Masato 
Published: April 2010

Abstract
The photochemical removal of benzene was investigated in N2/O2 mixtures (0–20% O2) using a 172 nm Xe2 excimer lamp at atmospheric pressure. After 20 min photoirradiation, about 97% of C6H6 (1000 ppm) in N2/O2 mixtures (10–20% O2) was converted to HCOOH, CO, and CO2. In the 172 nm photolysis of C6H6, not only direct photolysis by VUV photons but also reactions of O(3P,1D) and O3 can take part in the decomposition of C6H6. To examine effects of direct photolysis, C6H6 was decomposed in N2, whereas the contribution of O3 was studied by observing the O3 + C6H6 reaction. The contribution of O(1D) was examined by reducing the total pressure to suppress the collisional quenching of O(1D) by N2/O2 mixtures. It was found that the O(3P) + C6H6 reaction plays a significant role in the initial stage of the removal reaction of C6H6.
Calculations and Electronic Analyses of 55Mn and 13C Nuclear Magnetic Shielding Constants for Mn(CO)5X (X = H, F, Cl, Br, I, and CH3) and M(CO)(NH3)3 (M = Cr2+, Fe2+, Cu+, and Zn2+)
Authors: Tanimura Hirotaka , Kitahori Ayumi , Kuzuoka Chie , Honda Yasushi , Hada Masahiko 
Published: April 2010

Abstract
We calculated 55Mn and 13C magnetic shielding constants for Mn(CO)5X (X = H, F, Cl, Br, I, and CH3) and M(CO)(NH3)3 (M = Cr2+, Fe2+, Cu+, and Zn2+), respectively. For the first molecular group, we compared the calculated 55Mn chemical shifts with the experimental values, and clarified effects of the basis sets. The calculated magnetic shielding constants using the second-order Douglas–Kroll–Hess (DKH2) method showed good agreement with the experimental results. According to the atomic orbital (AO) contribution analysis, the origin of the chemical shifts was attributed to the d–d transitions of Mn. In particular, the 3dπ orbital mainly contributed to the paramagnetic term of the Mn chemical shift. For the second molecular group, the 13C chemical shifts were dependent on the metal atoms. When the metal centers were Cr2+ or Fe2+, lower field shifts were seen. When the metal centers were Cu+ or Zn2+, upper field shifts were observed. These results were in good agreement with the experimental trends. The change of the paramagnetic term mainly depended on the d orbital configurations of the metal of centers, and the donation from the metal d orbital to the CO anti-bonding π* orbitals is expected to affect the chemical shift.
Theoretical Study of Bond-Switching in 1,6-Dihydro-6a-thia-1,6-diazapentalene (10-S-3) Systems Compared with Corresponding Oxygen Analogues
Authors: Atsumi Teruo , Abe Tomohiro , Akiba Kin-ya , Nakai Hiromi 
Published: April 2010

Abstract
Theoretical study of the mechanism of bond-switching of 5-(1-aminoethylimino)-3-methyl-1,2,4-thiadiazole and 5-(2-aminovinyl)isothiazole was carried out by using simplified models of 1,6-dihydro-6a-thia-1,6-diazapentalene (10-S-3) systems and corresponding oxygen analogs. Geometries and energetics were examined along unimolecular and bimolecular reaction paths by hybrid density functional theory (DFT) calculations with triple-zeta class basis sets by taking into account solvent effects which is estimated by the polarizable continuum model. It was clarified that the unimolecular reactions cannot proceed due to the high energy barriers around 70 kcal mol−1. On the other hand, the bimolecular processes in neutral and acidic conditions can be accomplished for the sulfur compounds, not for the oxygen ones. The differences of the reactivities between the sulfur and oxygen compounds were found to be due to the difference of the stability of the symmetric intermediates with the hypervalent three-center four-electron bonds.
Finite Element Modeling of a Rockman Portable Dynamic Hardness Tester
Authors: Zareh H. , Martinez J. , Carter M. , Koenig J. 
Published: April 2010

Abstract
A Rockman hardness tester is a type of portable dynamic hardness tester that is similar to a standard Rockwell hardness tester, except the full load is applied dynamically over a very short duration. Finite element models were developed for a Rockman hardness tester and a standard B scale Rockwell hardness tester. The Rockwell hardness tester model served as a benchmark problem to validate assumptions and modeling techniques used for the Rockman hardness tester model. Before developing the model of the Rockman hardness tester, the dynamic loading characteristics were determined using a piezoelectric force transducer. After solving both models comparisons were drawn between the two hardness testers.
Person variations in Akhvakh verb morphology: functional motivation and origin of an uncommon pattern
Authors: Creissels Denis 
Published: April 2010

Abstract
In the Nakh-Daghestanian language family, person agreement is considered a recent innovation of a few isolated languages. Person variations in Akhvakh verb morphology are limited to the perfective positive and follow a typologically rare pattern, in which the same couple of verbal endings encodes a 1st person vs. 2nd/3rd person contrast in declarative clauses, and a 2nd person vs. 1st/3rd person contrast in questions. A comparison of the verb forms concerned by this distinction with other Akhvakh verb forms not involved in this mechanism suggests that, in Akhvakh, the emergence of this atypical pattern resulted from the reanalysis of a TAM distinction.
Absent arguments on the Absentive: an exercise in silent syntax. Grammatical category or just pragmatic inference?
Authors: Abraham Werner 
Published: April 2010

Abstract
It will be claimed that given the highly situationally restricted context triggering the Absentive meaning under any of the available construals, the occurrence of the Ab-sentive is not a grammatical category. Nor is there a viable diachronic relation with the PP-Progressive in German and other languages such as English. Admittedly, this leaves unaccounted for the fine gradual distance-semantic difference between the Bare Infinitive and the PP-Progressive in German. What appears to provide a further argument against the general categorical status of this construal is the fact that reading does not emerge under any construction type in the Slavic languages.
Susceptibility of Three Stocks of Pacific Herring to Viral Hemorrhagic Septicemia
Authors: Hershberger P. K. , Gregg J. L. , Grady C. A. , Collins R. M. , Winton J. R. 
Published: April 2010

Abstract
Laboratory challenges using specific-pathogen-free Pacific herring Clupea pallasii from three distinct populations indicated that stock origin had no effect on susceptibility to viral hemorrhagic septicemia (VHS). All of the populations were highly susceptible to the disease upon initial exposure, with significantly greater cumulative mortalities occurring in the exposed treatment groups (56.3–64.3%) than in the unexposed control groups (0.8–9.0%). Interstock differences in cumulative mortality were not significant. The virus loads in the tissues of fish experiencing mortality were 10–10,000 times higher during the acute phase of the epizootics (day 13 postexposure) than during the recovery phase (days 30–42). Survivors of the epizootics were refractory to subsequent VHS, with reexposure of VHS survivors resulting in significantly less cumulative mortality (1.2–4.0%) than among positive controls (38.1–64.4%); interstock differences in susceptibility did not occur after reexposure. These results indicate that data from experiments designed to understand the ecology of VHS virus in a given stock of Pacific herring are broadly applicable to stocks throughout the northeastern Pacific.
Temperature dependence of turn-on time delay of semiconductor laser diode: Theoretical analysis
Authors: Ab Rahman M.S. , Hassan M.R. 
Published: April 2010

AbstractTemperature dependence of the turn-on time delay (ton) of uncooled semiconductor laser diodes biased below and above threshold is analyzed in presence of data pattern effect. We show that even when the laser is biased at or slightly above threshold, the increase in temperature of operation will lead to increase in the threshold carrier (Nth) and consequently the laser diode will be biased below the threshold again and a significant value of ton will be produced. Thus, knowledge about a value of dc-bias current required to achieve zero ton within wide range of temperature degrees is important when considering uncooled laser diode in high-speed optical communication systems. The temperature dependence of ton is calculated according to the temperature dependence of Nth and Auger recombination coefficient (C) and not by the well-know exponentional relationship of threshold current with temperature. The temperature dependence of Nth is calculated according to the temperature dependence of laser cavity parameters. Advanced analytical model is derived in term of carrier density, recombination coefficients and the injection current (Iinj). The validity of proposed model is confirmed by a numerical method. In addition, approximated models are included where under specified assumptions the proposed model reduces to the well-known approximate models of ton. According to our typical values and at a specified value of modulation current, the dc-bias one (Iib) should be increased from Iib = Ith to Iib ≈ 1.25 and 1.5Ith in order to achieve approximately zero ton when the temperature increases from 25°C to 55°C and 85°C, respectively.