bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Conversation with Haldor Topsøe
Authors: Topsøe Haldor , Mavrikakis Manos 
Published: June 2012

Haldor Topsøe was born in Copenhagen, Denmark, in 1913. He studied chemical engineering at the Technical University of Denmark (DTU). In 1940, he founded the company Haldor Topsøe, which has become one of the most successful companies in the field of heterogeneous catalysis. The company develops and markets catalysts and processes for petroleum refining, air-pollution control, synthesis gas production, ammonia and methanol production and solid oxide fuel cells. The company Haldor Topsøe is also a leader in the production and state-of-the-art scientific characterization of new catalysts. Dr. Topsøe is currently the sole owner of the company. He has written numerous articles on ammonia synthesis, catalysis, and energy questions. He is the author of several books on economics. Dr. Topsøe has received numerous awards, including honorary doctorates from Aarhus University, DTU, and the Chalmers University in Sweden; the Gold Medal from the Royal Academy of Sciences; the Hoover Medal for his technical abilities and entrepreneurship; and the Grove Memorial Medal for Advances in Fuel Cell Technology. Topsøe is a member of the Danish and the Swedish Academies of Technical Sciences and of the U.S. National Academy of Engineering. The following interview was conducted on August 16, 2010. –Manos Mavrikakis
The Antibody-Based Delivery of Interleukin-12 to the Tumor Neovasculature Eradicates Murine Models of Cancer in Combination with Paclitaxel
Authors: Pasche Nadine , Wulhfard Sarah , Pretto Francesca , Carugati Elisa , Neri Dario 
Published: June 2012

AbstractPurpose: Interleukin-12 (IL12) is a potent proinflammatory cytokine with antitumor activity. Its heterodimeric nature makes it compatible with a large variety of different immunocytokine formats. Here we report the design, production, and characterization of a novel immunocytokine, based on the fusion of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin, a marker of tumor neovasculature) with IL12 (termed IL12-F8-F8).Experimental Design: We developed a novel immunocytokine based on the sequential fusion of interleukin-12 as a single polypeptide with two F8 antibodies in single-chain Fv (scFv) format. The fusion protein was characterized in vitro, and its targeting performance was assessed in vivo. The immunocytokine antitumor activity was studied as monotherapy as well as in combination therapies in three different murine tumor models. Moreover, depletion experiments and tumor analysis revealed a dominant role of natural killer cells for the mechanism of action.Results: IL12-F8-F8 can be produced in mammalian cells, yielding a product of good pharmaceutical quality, capable of selective localization on the tumor neovasculature in vivo, as judged by quantitative biodistribution analysis with radioiodinated protein preparations. The protein potently inhibited tumor growth in three different immunocompetent syngeneic models of cancer. The treatment was generally well tolerated. Moreover, the IL12-F8-F8 fusion protein could be produced both with murine IL12 (mIL12) and with human IL12 (hIL12).Conclusions: The potent antitumor activity of mIL12-F8-F8, studied alone or in combination with paclitaxel in different tumor models, paves the way to the clinical development of the fully human immunocytokine. Clin Cancer Res; 18(15); 4092–103. ©2012 AACR.
Breast Cancer Cell Targeting by Prenylation Inhibitors Elucidated in Living Animals with a Bioluminescence Reporter
Authors: Chinault Sharon L. , Prior Julie L. , Kaltenbronn Kevin M. , Penly Anya , Weilbaecher Katherine N. , Piwnica-Worms David , Blumer Kendall J. 
Published: June 2012

Abstract
Purpose: Inhibitors of protein prenylation, including prenyltransferase inhibitors and aminobisphosphonates such as zoledronic acid, are being investigated intensively as therapeutics in cancer and other diseases. Determining whether prenylation inhibitors directly or indirectly target tumor and/or host cells is key to understanding therapeutic mechanisms.
Experimental Design: To determine which cell types can be targeted directly by distinct classes of prenylation inhibitors in vivo, we describe herein the development and implementation of a sensitive and pharmacologically specific bioluminescence-based imaging reporter that is inducible by prenylation inhibitors.
Results: In mouse xenograft models of breast cancer, using reporter-bearing mammary fat pad- or bone-localized tumor cells, we show that a prenyltransferase inhibitor robustly induces reporter activity in vivo. In contrast, zoledronic acid, a bone-associated aminobisphosphonate that exerts adjuvant chemotherapeutic activity in patients with breast cancer, fails to induce reporter activity in tumor cells of either model.
Conclusions: Although a prenyltransferase inhibitor can directly target breast cancer cells in vivo, zoledronic acid and related aminobisphosphonates are likely to exert antitumor activity indirectly by targeting host cells. Accordingly, these findings shift attention toward the goal of determining which host cell types are targeted directly by aminobisphosphonates to exert adjuvant chemotherapeutic activity. Clin Cancer Res; 18(15); 4136–44. ©2012 AACR.
Glycine Exerts Dual Roles in Ischemic Injury Through Distinct Mechanisms
Authors: Yao Wen , Ji Fang , Chen Zheng , Zhang Nan , Ren Si-Qiang , Zhang Xiao-Yan , Liu Su-Yi , Lu Wei 
Published: June 2012

Background and Purpose—
We characterized the differential effects of glycine at different levels in the induction of postischemic long-term potentiation, as well as in the neuronal damage induced by focal ischemia.

Methods—
Whole-cell patch clamp recordings were obtained from rat hippocampal slice preparations. In vitro ischemia and postischemic long-term potentiation were induced by oxygen and glucose deprivation. In vivo ischemia was induced by transient middle cerebral artery occlusion.

Results—

In both in vitro and in vivo ischemia models, glycine at low level exerts deleterious effects in postischemic long-term potentiation and ischemic neuronal injury by modulation of the N-methyl-
d
-aspartate receptor coagonist site; whereas glycine at high level exerts neuroprotective effects by activation of glycine receptor and subsequent differential regulation of N-methyl-
d
-aspartate receptor subunit components.

Conclusions—
Our results provide a molecular basis for the dual roles of glycine in ischemic injury through distinct mechanisms, and they suggest that glycine receptors could be a potential target for clinical treatment of stroke.
Long-term Excess Mortality in Pediatric Patients With Cerebral Aneurysms
Authors: Koroknay-Pál Päivi , Laakso Aki , Lehto Hanna , Seppä Karri , Kivisaari Riku , Hernesniemi Juha , Niemelä Mika 
Published: June 2012

Background and Purpose—
Knowledge of the long-term excess mortality in pediatric aneurysm patients is lacking. The aim of this study was to assess the long-term excess mortality of 102 pediatric patients with cerebral aneurysm treated at the department of neurosurgery at Helsinki University Central Hospital between 1937 and 2009.

Methods—
Patients were followed from diagnosis until death or the end of the year 2010. Relative survival ratio provided the measure of excess mortality in these patients compared with mortality of the general Finnish population matched by age, sex, and calendar time.

Results—
A majority of the patients (n=89) presented with subarachnoid hemorrhage. Aneurysms (n=118) were treated operatively (n=79), endovascularly (n=1), or conservatively (n=36). The mean follow-up time was 26.8 years (range, 0–55.6 years). By the end of follow-up, 34 of the 102 patients had died; 26 of these deaths (76%) were aneurysm-related. There was overall excess mortality of 10% (cumulative relative survival ratio, 0.90; 95% CI, 0.80–0.96) and 19% (cumulative relative survival ratio, 0.81; 95% CI, 0.66–0.91) at 20 and 40 years after the diagnosis among the 1-year subarachnoid hemorrhage survivors, respectively. The excess mortality was particularly high in boys. There was no long-term excess mortality among patients with unruptured aneurysms. Aneurysm-related deaths included rebleedings from open or partially occluded aneurysms, epileptic seizures, de novo and recurrent aneurysms, or sequelae of subarachnoid hemorrhage.

Conclusions—
There is long-term excess mortality in pediatric patients with aneurysm even decades after successful treatment of a ruptured aneurysm, especially among boys. The excess mortality is mainly aneurysm-related.
A New Approach to Modeling Vehicle-Induced Heat and Its Thermal Effects on Road Surface Temperature
Authors: Fujimoto Akihiro , Saida Akira , Fukuhara Teruyuki 
Published: June 2012

AbstractThe distribution of vehicle-induced wind velocity in the transversal direction of roads is measured. A statistical analysis is also performed to find the vehicle stopping time and stopping position at traffic signals. These results are used to build a heat-balance model to predict the road surface temperature resulting from the thermal effects of vehicles. To validate the model, measured and calculated road surface temperatures for a free-running (single path) location and a traffic-signal location are compared. The contributions of meteorological and vehicle-induced heat fluxes to the road surface temperature are quantitatively analyzed. For the present traffic and meteorological conditions, the calculated and measured road surface temperatures were in agreement for both the free-running and traffic-signal locations. Furthermore, the thermal contribution of vehicles to the road surface temperature was found to be nonnegligible at both locations.
Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine
Authors: Pallikkuth Suresh , Parmigiani Anita , Silva Sandra Y. , George Varghese K. , Fischl Margaret , Pahwa Rajendra , Pahwa Savita 
Published: June 2012

Abstract
The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5+ CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and CD4 T-cell loss are recognized features of HIV infection, in the present study, we investigated pTFH cells in 25 HIV-infected patients on antiretroviral therapy. pTFH frequency was equivalent in patients and healthy controls (HCs), and these cells displayed a central memory phenotype. Sixteen patients and 8 HCs in this group were given a single dose of H1N1/09 influenza vaccine during the 2009 H1N1 influenza outbreak. In the vaccine responders (n = 8) and HCs, pTFH cells underwent expansion with increased IL-21 and CXCL13 secretion in H1N1-stimulated PBMC culture supernatants at week 4 (T2). These changes were not seen in vaccine nonresponders (n = 8). In coculture experiments, sorted pTFH cells supported HIN1-stimulated IgG production by autologous B cells only in vaccine responders. At T2, frequencies of pTFH were correlated with memory B cells, serum H1N1 Ab titers, and Ag-induced IL-21 secretion. Characterization of pTFH cells may provide additional insight into cellular determinants of vaccine-induced Ab response, which may have relevance for vaccine design.
Differential mRNA expression of seven genes involved in cholesterol metabolism and transport in the liver of atherosclerosis-susceptible and -resistant Japanese quail strains
Authors: Li Xinrui , Schulte Patricia , Godin David V , Cheng Kimberly M 
Published: June 2012

Abstract

Background
Two atherosclerosis-susceptible and -resistant Japanese quail (Coturnix japonica) strains obtained by divergent selection are commonly used as models to study atherosclerosis, but no genetic characterization of their phenotypic differences has been reported so far. Our objective was to examine possible differences in the expression of genes involved in cholesterol metabolism and transport in the liver between these two strains and to evaluate the value of this model to analyze the gene system affecting cholesterol metabolism and transport.

Methods
A factorial study with both strains (atherosclerosis-susceptible versus atherosclerosis-resistant) and two diets (control versus cholesterol) was carried out. The mRNA concentrations of four genes involved in cholesterol biosynthesis (HMGCR, FDFT1, SQLE and DHCR7) and three genes in cholesterol transport (ABCG5, ABCG8 and APOA1) were assayed using real-time quantitative PCR. Plasma lipids were also assayed.

Results
Expression of ABCG5 (control diet) and ABCG8 (regardless of dietary treatment) and expression of HMGCR, FDFT1 and SQLE (regardless of dietary treatment) were significantly higher in the atherosclerosis-resistant than in the atherosclerosis-susceptible strain. Plasma triglyceride and LDL levels, and LDL/HDL ratio were significantly higher in the atherosclerosis-susceptible than in the atherosclerosis-resistant strain fed the cholesterol diet. In the atherosclerosis-susceptible strain, ABCG5 expression regressed significantly and positively on plasma LDL level, whereas DHCR7 and SQLE expression regressed significantly and negatively on plasma triglyceride level.

Conclusions
Our results provide support for the hypothesis that the atherosclerosis-resistant strain metabolizes and excretes cholesterol faster than the atherosclerosis-susceptible strain. We have also demonstrated that these quail strains are a useful model to study cholesterol metabolism and transport in relation with atherosclerosis.
Identification and characterization of peptide: N- glycanase from Dictyostelium discoideum
Authors: Gosain Anuradha , Lohia Rakhee , Shrivastava Anju , Saran Shweta 
Published: June 2012

Abstract

Background
Peptide: N- glycanase (PNGase) enzyme cleaves oligosaccharides from the misfolded glycoproteins and prepares them for degradation. This enzyme plays a role in the endoplasmic reticulum associated degradation (ERAD) pathway in yeast and mice but its biological importance and role in multicellular development remain largely unknown.

Results
In this study, the PNGase from the cellular slime mold, Dictyostelium discoideum (Dd PNGase) was identified based on the presence of a common TG (transglutaminase) core domain and its sequence homology with the known PNGases. The domain architecture and the sequence comparison validated the presence of probable functional domains in Dd PNGase. The tertiary structure matched with the mouse PNGase. Here we show that Dd PNGase is an essential protein, required for aggregation during multicellular development and a knockout strain of it results in small sized aggregates, all of which did not form fruiting bodies. The in situ hybridization and RT-PCR results show higher level of expression during the aggregate stage. The expression gets restricted to the prestalk region during later developmental stages. Dd PNGase is a functional peptide:N-glycanase enzyme possessing deglycosylation activity, but does not possess any significant transamidation activity.

Conclusions
We have identified and characterized a novel PNGase from D. discoideum and confirmed its deglycosylation activity. The results emphasize the importance of PNGase in aggregation during multicellular development of this organism.
β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE) and remains active in selected postnatal OSE cells
Authors: Usongo Macalister , Farookhi Riaz 
Published: June 2012

Abstract
Background
Wnts are a family of secreted signaling molecules involved in a number of developmental processes including the establishment of cell fate, polarity and proliferation. Recent studies also implicate wnts in epithelial adult stem cell maintenance, renewal and differentiation. Wnts transduce their signal through one of three signaling pathways. The best studied, the wnt/β-catenin pathway, leads to an increase in intracellular β-catenin which acts as a co-transcription factor with members of the Tcf/Lef family. A number of wnts are expressed in the ovary, specifically in the membrana granulosa and ovarian surface epithelium (OSE). We investigated the spatio-temporal pattern of β-catenin/Tcf expression in the OSE using responsive transgenic (TopGal) mice.

Results
The generated β-galactosidase response (lacZ+) identified the cell population that overlies the medio-lateral surface of the indifferent gonad at embryonic day (E) 11.5. From E12.5 onwards, lacZ expression disappeared in cells covering the testis but remained with ovary development. LacZ+ OSE cells were present throughout embryonic and postnatal ovarian development but demonstrated an age-dependent decrease to a small proportion when animals were weaned and remained at this proportion with aging. Flow cytometric (FACS) and ovarian section analyses showed lacZ+ cells constitute approximately 20% of OSE in postnatal (day 1) mice which fell to 8% in 5 day-old animals while in prepubertal and adult mice this accounted for only 0.2% of OSE. Apoptosis was undetected in OSE of neonates and β-catenin/Tcf-signaling cells were proliferative in neonatal mice indicating that neither cell death nor proliferation failure was responsible for the proportion alteration. It appeared that lacZ+ cells give rise to lacZ- cells and this was confirmed in cell cultures. The DNA-binding dye DyeCycle Violet was used to set up the side population (SP) assay aimed at identifying subpopulations of OSE cells with chemoresistance phenotype associated with ABCG2 transporter activity. FACS analysis revealed lacZ+ cells exhibit cytoprotective mechanisms as indicated by enrichment within the SP.

Conclusions
The study raises the possibility that wnt/β-catenin-signaling cells constitute a progenitor cell population and could underlie the pronounced histopathology observed for human ovarian cancer.
Sweat output measurement of the post-ganglion sudomotor response by Q-Sweat Test: a normative database of Chinese individuals
Authors: Chen Shu-Fang , Chang Ya-Ting , Lu Cheng-Hsien , Huang Chi-Ren , Tsai Nei-Wen , Chang Chiung-Chih , Huang Chih-Cheng , Chuang Yao-Chung , Chang Wen-Neng 
Published: June 2012

AbstractBackgroundQ-Sweat is a model used for evaluating the post-ganglionic sudomotor function by assessing sweat response. This study aimed to establish the normative database of Q-Sweat test among Chinese individuals since this type of information is currently lacking.ResultsOne hundred and fifty (150) healthy volunteers, 76 men and 74 women with age range of 22–76 years were included. Skin temperature and sweat onset latency measured at the four sites (i.e., the forearm, proximal leg, distal leg, and the foot) did not significantly correlate with age, gender, body height (BH), body weight (BW), and body mass index (BMI) but the total sweat volume measured in all four sites significantly correlated with sex, BH, and BW. Except for the distal leg, the total sweat volume measured at the other three sites had a significant correlation with BMI. In terms of gender, men had larger total sweat volume, with median differences at the forearm, proximal leg, distal leg, and foot of 0.591 μl, 0.693 μl, 0.696 μl, and 0.358 μl, respectively. Regarding BW difference (≥62 and < 62 Kg), those with BW ≥62 Kg had larger total sweat volume. Median differences at the forearm, proximal leg, distal leg, and foot were 0.538 μl, 0.744 μl, 0.695 μl, and 0.338 μl, respectively. There was an uneven distribution of male and female participants in the two BW groups. In all conditions, the total sweat volume recorded at the foot site was the smallest.ConclusionThis is the first report to show the normative database of sweat response in Chinese participants evaluated using Q-Sweat device. This normative database can help guide further research on post-ganglionic sudomotor or related clinical practice involving a Chinese population.
The organ-specific expression of terpene synthase genes contributes to the terpene hydrocarbon composition of chamomile essential oils
Authors: Irmisch Sandra , Krause Sandra T , Kunert Grit , Gershenzon Jonathan , Degenhardt Jörg , Köllner Tobias G 
Published: June 2012

Abstract

Background
The essential oil of chamomile, one of the oldest and agronomically most important medicinal plant species in Europe, has significant antiphlogistic, spasmolytic and antimicrobial activities. It is rich in chamazulene, a pharmaceutically active compound spontaneously formed during steam distillation from the sesquiterpene lactone matricine. Chamomile oil also contains sesquiterpene alcohols and hydrocarbons which are produced by the action of terpene synthases (TPS), the key enzymes in constructing terpene carbon skeletons.

Results
Here, we present the identification and characterization of five TPS enzymes contributing to terpene biosynthesis in chamomile (Matricaria recutita). Four of these enzymes were exclusively expressed in above-ground organs and produced the common terpene hydrocarbons (−)-(E)-β-caryophyllene (MrTPS1), (+)-germacrene A (MrTPS3), (E)-β-ocimene (MrTPS4) and (−)-germacrene D (MrTPS5). A fifth TPS, the multiproduct enzyme MrTPS2, was mainly expressed in roots and formed several Asteraceae-specific tricyclic sesquiterpenes with (−)-α-isocomene being the major product. The TPS transcript accumulation patterns in different organs of chamomile were consistent with the abundance of the corresponding TPS products isolated from these organs suggesting that the spatial regulation of TPS gene expression qualitatively contribute to terpene composition.

Conclusions
The terpene synthases characterized in this study are involved in the organ-specific formation of essential oils in chamomile. While the products of MrTPS1, MrTPS2, MrTPS4 and MrTPS5 accumulate in the oils without further chemical alterations, (+)-germacrene A produced by MrTPS3 accumulates only in trace amounts, indicating that it is converted into another compound like matricine. Thus, MrTPS3, but also the other TPS genes, are good markers for further breeding of chamomile cultivars rich in pharmaceutically active essential oils.
Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy
Authors: Yen Hsu-Heng , Yang Chia-Wei , Su Wei-Wen , Soon Maw-Soan , Wu Shun-Sheng , Lin Hwai-Jeng 
Published: June 2012

Abstract

Background
High dose intravenous proton pump inhibitor after endoscopic therapy for peptic ulcer bleeding has been recommended as adjuvant therapy. Whether oral proton pump inhibitor can replace intravenous proton pump inhibitor in this setting is unknown. This study aims to compare the clinical efficacy of oral and intravenous proton pump inhibitor after endoscopic therapy.

Methods
Patients with high-risk bleeding peptic ulcers after successful endoscopic therapy were randomly assigned as oral lansoprazole or intravenous esomeprazole group. Primary outcome of the study was re-bleeding rate within 14 days. Secondary outcome included hospital stay, volume of blood transfusion, surgical intervention and mortality within 1 month.

Results
From April 2010 to Feb 2011, 100 patients were enrolled in this study. The re-bleeding rates were 4% (2/50) in the intravenous group and 4% (2/50) in the oral group. There was no difference between the two groups with regards to the hospital stay, volume of blood transfusion, surgery or mortality rate. The mean duration of hospital stay was 1.8 days in the oral lansoprazole group and 3.9 days in the intravenous esomeprazole group (p > 0.01).

Conclusion
Patients receiving oral proton pump inhibitor have a shorter hospital stay. There is no evidence of a difference in clinical outcomes between oral and intravenous PPI treatment. However, the study was not powered to prove equivalence or non-inferiority. Future studies are still needed.

Trial registration
NCT01123031