bluuebunny/crossref_metadata_2025 huggingface dataset:
Energieeinsparpotential eines Passivhauses unter Berücksichtigung von Wetterprognosen
Authors: Hettfleisch Christian , Ledinger Stephan , Dubisch Florian , Zucker Gerhard , Palensky Peter
Published: November 2010

Innovative Regelungen in Gebäuden können beachtliche Energieeinsparungen zur Folge haben. Besonderes Augenmerk ist hierbei auf Gebäude gelegt, die in einem gesteigerten Maße von ihrer Umwelt thermisch entkoppelt sind: dazu wird ein nach Passivhausstandard gebautes, real existierendes Bürogebäude modelliert, das Modell mit Monitoring‐Daten validiert und simuliert. Anhand der Simulationen mit der Simulationsumgebung TRNSYS und der Hinzunahme von gemessenen Wetterdaten werden mögliche Energieeinsparpotentiale erkannt und ausgewertet. In dieser Betrachtung, die den Zeitraum eines kompletten Jahres (Zeitraum 2009/2010) beinhaltet, liegt der Fokus auf Energieeinsparungen, die durch intelligentes Heizen und Kühlen des Gebäudes erzielt werden können.

Potential for saving energy in a Passivhaus building, taking into account weather forecasts. Innovative controls in buildings can lead to remarkable energy savings. The main focus of this paper is on buildings that are highly thermally insulated from their environment: the model is based on an existing building that was built to Passivhaus standard, and then validated with monitoring data and simulated. By adding actual, measured weather data in the simulations (which were done in the TRNSYS simulation environment) potential energy savings are identified and evaluated. In this analysis, which covers a full year (2009/2010), we concentrate on energy savings in the building’s heating and cooling systems.
Der neue DIN‐Fachbericht 4108‐8 Vermeidung von Schimmelwachstum in Wohngebäuden
Authors: Spitzner Martin H.
Published: November 2010

Zunehmend wird wieder von Problemen des Schimmelpilzwachstums in Wohngebäuden berichtet. Die Baukonstruktion eines Wohngebäudes muss die Voraussetzung schaffen, dass bei üblicher, bestimmungsgemäßer Nutzung der Räume die Innenoberflächen der Bauteile so warm und trocken bleiben, dass Schimmelpilzwachstum vermieden wird. Gegebenenfalls sind entsprechende Wärmedämm‐ und anlagentechnische Sanierungsmaßnahmen erforderlich. Gleichzeitig muß das Nutzerverhalten den baukonstruktiven und nutzungsbedingten Gegebenheiten angepasst sein. Dazu gehört eine gleichmäßige Beheizung, eine ausreichende Belüftung, eine weitgehend ungehinderte Luftzirkulation durch entsprechende Möblierung, sowie eine nicht ungemessen hohe Feuchtefreisetzung. Der DIN‐Fachbericht 4108‐8 “Wärmeschutz und Energieeinsparung in Gebäuden — Teil 8: Vermeidung von Schimmelwachstum in Wohngebäuden” fasst die Einflussfaktoren Baukonstruktion, Heizung, Lüftung, Nutzung/Nutzerverhalten zu einer ganzheitlichen Betrachtung zusammen. Er hilft bei der Klärung von Ursachen und bei der Einleitung von Gegenmaßnahmen.

Avoiding mould growth in dwellings — the new report on DIN 4108‐8. Problems with mould growth in residential buildings are an increasing occurrence. The construction of a dwelling house should ensure that, provided rooms are used in accordance with the design purpose, the internal surfaces of the building components stay sufficiently warm and dry so that mould growth is avoid ed. Where this is not the case, remedial measures have to be undertaken, such as installing additional insulation and/or ventilation/ heating devices. But it is equally important that the behaviour of the users of a building is appropriate for the design of the building. This includes evenly distributed space heating, adequate ventilation, air circulation that is largely unobstructed by furniture, and that moisture release in the dwelling is not excessive. The report on DIN 4108‐8 ‘Thermal insulation and conserving energy in buildings — Part 8: Avoiding mould growth in dwellings’ takes a comprehensive look at all relevant factors, such as construction details, heating and ventilation systems, and user behaviour. The report helps to clarify the causes of problems and makes suggestions for remedial actions.
Vom Niedrigenergie‐ zum Nullenergiehaus: Standortbestimmung und Entwicklungsperspektiven
Authors: Voss Karsten , Musall Eike , Lichtmeß Markus
Published: November 2010

Der Begriff “Nullenergiehaus” ist in den letzten Jahren national und international zum Inbegriff für die konsequente Zusammenführung von Maßnahmen zur drastischen Energieeinsparung und optimierter dezentraler Nutzung erneuerbarer Energien geworden. Dabei geht es nicht um energieautarke Gebäude und die dabei große Herausforderung der saisonalen Energiespeicherung. Grundidee ist, dass die von einem Gebäude in ein Netz eingespeiste Energiemenge in der Jahresbilanz mindestens dem Energiebezug entspricht. Plusenergiehäuser erzielen eine positive Bilanz. Trotz Verankerung in zahlreichen energiepolitischen Positionspapieren existiert aber bisher keine Definition oder normative Beschreibung. Der Beitrag erläutert in einem internationalen Kontext die Hintergründe und diskutiert die Einflussgrößen bei der Bilanzierung. Nach Darstellung der normativen Berechnungszusammenhänge wird eine abgestimmte Terminologie und nationale Vorgehensweise vorgeschlagen. Diese berücksichtigt neben der Energiebilanz die Energieeffizienz und die Eigenbedarfsdeckung.

From Low‐Energy to Zero‐Energy Building: Status and Perspectives. ”Net Zero Energy Building” has become a prominent wording to describe the synergy of energy efficient building and renewable energy utilization to reach a balanced energy budget over a yearly cycle. Taking into account the energy exchange with a grid infrastructure overcomes the limitations of energy autonomous buildings with the need for seasonal energy storage on‐site. Even though the wording ”Net Zero Energy Building” occurs in many energy policy documents a harmonized definition or a balancing method is still missing. The paper reports on the background and the various effects influencing the energy balance approach. After discussing the national energy code framework in Germany a harmonized terminology and balancing procedure is suggested. Besides the energy balance the procedure takes load energy efficiency and matching into account.
In situ generation of hydrogen peroxide by carbohydrate oxidase and cellobiose dehydrogenase for bleaching purposes
Authors: Pricelius Sina , Ludwig Roland , Lant Neil J. , Haltrich Dietmar , Guebitz Georg M.
Published: November 2010

The carbohydrate oxidase from Microdochium nivale (CAOX), heterologously expressed in Aspergillus oryzae, and cellobiose dehydrogenase from Myriococcum thermophilum (MtCDH), were assessed for their ability to generate bleaching species at a pH suitable for liquid detergents. The substrate specificities of CAOX and MtCDH were analyzed on a large variety of soluble and insoluble substrates, using oxygen as an electron receptor. Even insoluble substrates like cellulose were oxidized from both CAOX and MtCDH, but only MtCDH produced H2O2 on cotton as the sole substrate. To enhance the amount of cello‐oligosaccharides formed from cotton as substrates for CAOX and MtCDH, various cellulases were used in combination with MtCDH or CAOX, leading to a 10‐fold increase in H2O2. As model substrates for colored stains, the degradation of pure anthocyanins and stain removal of blueberry stains by CAOX and MtCDH was examined in the absence and presence of a horseradish peroxidase. Both enzymes were able to produce an amount of H2O2 sufficient to decolorize the pure anthocyanins within 2 h and showed significant cleaning benefits on the stains.
Structure and Function of Mammalian DNA Methyltransferases
Authors: Jurkowska Renata Zofia , Jurkowski Tomasz Piotr , Jeltsch Albert
Published: November 2010

DNA methylation plays an important role in epigenetic signalling, having an impact on gene regulation, chromatin structure, development and disease. Here, we review the structures and functions of the mammalian DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b, including their domain structures, catalytic mechanisms, localisation, regulation, post‐translational modifications and interaction with chromatin and other proteins, summarising data obtained in genetic, cell biology and enzymatic studies. We focus on the question of how the molecular and enzymatic properties of these enzymes are connected to the dynamics of DNA methylation patterns and to the roles the enzymes play in the processes of de novo and maintenance DNA methylation. Recent enzymatic and genome‐wide methylome data have led to a new model of genomic DNA methylation patterns based on the preservation of average levels of DNA methylation in certain regions, rather than the methylation states of individual CG sites.
Supramolecular Organization of Light‐Harvesting Porphyrin Macrorings
Authors: Satake Akiharu , Azuma Shintaro , Kuramochi Yusuke , Hirota Shun , Kobuke Yoshiaki
Published: November 2010

Porphyrin‐based supramolecular nanostructures have been produced by the self‐assembly of porphyrin macrorings with three benzoic acid groups (Acid‐R) on each side of the rings through cooperative carboxyl–carboxyl hydrogen bonds. Structures of the organized Acid‐R were analyzed by AFM, and two clear distribution peaks were observed at 3 and 27 nm in the height‐distribution histogram. From the overall assessment, the higher objects are considered to be one‐dimensional structures standing vertically on the mica substrate. The height corresponds to an 11‐mer of a unit Acid‐R. Light‐harvesting functions were examined by using fluorescence titration, whereby an energy‐acceptor molecule (Tripod 2) was employed that strongly interacted with Acid‐R units (association constant: 2.0×108 M−1), specifically from the inner pore. The titration results showed that the apparent stoichiometry [Tripod 2]/[Acid‐R] was <0.5, and that the value was concentration dependent. Titration results reasonably account for the scheme in which Tripod 2 only interacts with each terminal in the organized Acid‐R. The number of organization was fitted to a 10‐mer of Acid‐R in a 6.8×10−7 M solution, and was consistent with that estimated from the AFM results. In the composites of organized Acid‐R/Tripod 2, a singlet excitation energy transfer occurred among the Acid‐R units, and to Tripod 2. The energy‐transfer rate constants were estimated by using the decamer model, which employed kinetic parameters obtained from steady‐state and time‐resolved fluorescence experiments.
Site‐Directed Spin‐Labeling of DNA by the Azide–Alkyne ‘Click’ Reaction: Nanometer Distance Measurements on 7‐Deaza‐2′‐deoxyadenosine and 2′‐Deoxyuridine Nitroxide Conjugates Spatially Separated or Linked to a ‘dA‐dT’ Base Pair
Authors: Ding Ping , Wunnicke Dorith , Steinhoff Heinz‐Jürgen , Seela Frank
Published: November 2010

Nucleobase‐directed spin‐labeling by the azide‐alkyne ‘click’ (CuAAC) reaction has been performed for the first time with oligonucleotides. 7‐Deaza‐7‐ethynyl‐2′‐deoxyadenosine (1) and 5‐ethynyl‐2′‐deoxyuridine (2) were chosen to incorporate terminal triple bonds into DNA. Oligonucleotides containing 1 or 2 were synthesized on a solid phase and spin labeling with 4‐azido‐2,2,6,6‐tetramethylpiperidine 1‐oxyl (4‐azido‐TEMPO, 3) was performed by post‐modification in solution. Two spin labels (3) were incorporated with high efficiency into the DNA duplex at spatially separated positions or into a ‘dA‐dT’ base pair. Modification at the 5‐position of the pyrimidine base or at the 7‐position of the 7‐deazapurine residue gave steric freedom to the spin label in the major groove of duplex DNA. By applying cw and pulse EPR spectroscopy, very accurate distances between spin labels, within the range of 1–2 nm, were measured. The spin–spin distance was 1.8±0.2 nm for DNA duplex 17(dA*7,10)⋅11 containing two spin labels that are separated by two nucleotides within one individual strand. A distance of 1.4±0.2 nm was found for the spin‐labeled ‘dA‐dT’ base pair 15(dA*7)⋅16(dT*6). The ‘click’ approach has the potential to be applied to all four constituents of DNA, which indicates the universal applicability of the method. New insights into the structural changes of canonical or modified DNA are expected to provide additional information on novel DNA structures, protein interaction, DNA architecture, and synthetic biology.
Simultaneous analysis of tramadol, O‐desmethyltramadol, and N‐desmethyltramadol enantiomers in rat plasma by high‐performance liquid chromatography‐tandem mass spectrometry: Application to pharmacokinetics
Authors: Godoy Ana Leonor Pardo Campos , De Moraes Natália Valadares , Martinez Edson Zangiacomi , Carvalho Teresa Maria De Jesus Ponte , Marques Maria Paula , Lanchote Vera Lucia
Published: November 2010

Tramadol (T) is available as a racemic mixture of (+)‐trans‐T and (−)‐trans‐T. The main metabolic pathways are O‐demethylation and N‐demethylation, producingtrans‐O‐desmethyltramadol (M1) andtrans‐N‐desmethyltramadol (M2) enantiomers, respectively. The analgesic effect of T is related to the opioid activity of (+)‐trans‐T and (+)‐M1and to the monoaminergic action of (+/−)‐trans‐T. This is the first study using tandem mass spectrometry as a detection system for the simultaneous analysis oftrans‐T,M1, andM2enantiomers. The analytes were resolved on a Chiralpak® AD column using hexane:ethanol (95.5:4.5, v/v) plus 0.1% diethylamine as the mobile phase. The quantitation limits were 0.5 ng/ml fortrans‐T andM1and 0.1 ng/ml forM2. The method developed and validated here was applied to a pharmacokinetic study in rats. Male Wistar rats (n= 6 at each time point) received a single oral dose of 20 mg/kg racemictrans‐T. Blood samples were collected up to 12 h after drug administration. The kinetic disposition oftrans‐T andM2was enantioselective (AUC(+)/(−)ratio = 4.16 and 6.36, respectively). The direction and extent of enantioselectivity in the pharmacokinetics oftrans‐T andM2in rats were comparable to data previously reported for healthy volunteers, suggesting that rats are a suitable model for enantioselective studies oftrans‐T pharmacokinetics. Chirality, 2011. © 2010 Wiley‐Liss, Inc.
Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer
Authors: Choi Chel Hun , Lee Yoo‐Young , Song Tae‐Jong , Park Hwang‐Shin , Kim Min Kyu , Kim Tae‐Joong , Lee Jeong‐Won , Lee Je‐Ho , Bae Duk‐Soo , Kim Byoung‐Gie
Published: November 2010

BACKGROUND:

Belotecan (CKD602; Camtobell, Chong Keun Dang Corp., Seoul, Korea) is a recently developed camptothecin derivative with antitumor properties. This phase II study was designed to evaluate the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC).

METHODS:

Thirty‐eight patients with recurrent EOC were treated with belotecan 0.3 mg/m2/day (days 1‐5) and carboplatin AUC 5 (day 5) every 3 weeks for 6 cycles. The primary objective was to determine the response rate as defined by Response Evaluation Criteria in Solid Tumors and CA‐125 response. Other end points included toxicities and progression‐free survival (PFS).

RESULTS:

All 38 patients were assessed for toxicity, and 35 patients were assessed for response. The overall response rate was 57.1%; there were 7 complete responses (20.0%), 13 partial responses (37.1%), 6 patients with stable disease (17.1%), and 9 patients with progressive disease (25.7%). Grades 3 and 4 hematologic toxicities included neutropenia (28.8%), thrombocytopenia (19.8%), and anemia (14.4%), and there were 2 episodes of febrile neutropenia. Median PFS was 7 months, with a median follow‐up of 12 months.

CONCLUSIONS:

The newly developed topoisomerase I inhibitor belotecan (CKD‐602) combined with carboplatin is a well‐tolerated regimen with activity in recurrent EOC. Further testing of this regimen is warranted to further characterize efficacy and indications for use. Cancer 2011. © 2010 American Cancer Society.
Radiation‐induced osteosarcomas of the calvarium and skull base
Authors: Patel Akash J. , Rao Vikas Y. , Fox Benjamin D. , Suki Dima , Wildrick David M. , Sawaya Raymond , DeMonte Franco
Published: November 2010

BACKGROUND:

Although a rare complication of ionizing radiation, radiation‐induced osteosarcoma is now more frequently recognized as radiation therapy has become common and cancer survival has increased. To date, publications on radiation‐induced osteosarcoma of the cranium are limited to a few small series and case reports.

METHODS:

Data from 175 patients with a history of sarcoma of the head at The University of Texas M. D. Anderson Cancer Center from 1975 to 2007 were reviewed to identify patients with radiation‐induced osteosarcoma. The diagnostic criteria were: 1) osteosarcoma arose within the previously irradiated field; 2) new sarcoma was histologically distinct from the original neoplasm; 3) no evidence of new sarcoma at the time of radiation; and 4) distinct latency period could be recognized. Frequencies and descriptive statistics were obtained for the various characteristics under study.

RESULTS:

The authors identified 16 patients with radiation‐induced osteosarcoma of the cranium at their institution. The average age at diagnosis was 35 years. The median latency period was 12.5 years. Nine patients had skull base tumors, and 7 had calvarial tumors. Of the 14 patients treated surgically, 86% developed local recurrence. The median survival time was 29 months, and the 5‐year survival rate was 29.6%.

CONCLUSIONS:

The authors report the largest series of cranial radiation‐induced osteosarcoma. Although radiation‐induced osteosarcoma is an uncommon but dire complication of radiotherapy, its incidence will probably increase in the future as the frequency of radiation treatment and cancer survival increase. These tumors are locally aggressive, and despite aggressive surgical and medical management, they have a high rate of local recurrence and mortality. Cancer 2011. © 2010 American Cancer Society.
Metabolic surgery and cancer
Authors: Ashrafian Hutan , Ahmed Kamran , Rowland Simon P. , Patel Vanash M. , Gooderham Nigel J. , Holmes Elaine , Darzi Ara , Athanasiou Thanos
Published: November 2010

The worldwide epidemic of obesity and the global incidence of cancer are both increasing. There is now epidemiological evidence to support a correlation between obesity, weight gain, and some cancers. Metabolic or bariatric surgery can provide sustained weight loss and reduced obesity‐related mortality. These procedures can also improve the metabolic profile to decrease cardiovascular risk and resolve diabetes in morbidly obese patients. The operations offer several physiological steps, the so‐called BRAVE effects: 1) bile flow alteration, 2) reduction of gastric size, 3) anatomical gut rearrangement and altered flow of nutrients, 4) vagal manipulation and 5) enteric gut hormone modulation. Metabolic operations are also associated with a significant reduction of cancer incidence and mortality. The cancer‐protective role of metabolic surgery is strongest for female obesity‐related tumors; however, the underlying mechanisms may involve both weight‐dependent and weight‐independent effects. These include the improvement of insulin resistance with attenuation of the metabolic syndrome as well as decreased oxidative stress and inflammation in addition to the beneficial modulation of sex steroids, gut hormones, cellular energetics, immune system, and adipokines. Elucidating the precise metabolic mechanisms of cancer prevention by metabolic surgery can increase our understanding of how obesity, diabetes, and metabolic syndrome are associated with cancer. It may also offer novel treatment strategies in the management of tumor generation and growth. Cancer 2011. © 2010 American Cancer Society.
Metabolic risk factors in prostate cancer
Authors: Chu David I. , Freedland Stephen J.
Published: November 2010

The biology of prostate cancer is influenced by the metabolic profile of each individual. The authors examined available evidence on interlinking prostate cancer with obesity, diabetes, and other metabolic syndrome components. See related article pp.
Concomitant ABCG2 overexpression and FLT3‐ITD mutation identify a subset of acute myeloid leukemia patients at high risk of relapse
Authors: Tiribelli Mario , Geromin Antonella , Michelutti Angela , Cavallin Margherita , Pianta Annalisa , Fabbro Dora , Russo Domenico , Damante Giuseppe , Fanin Renato , Damiani Daniela
Published: November 2010

BACKGROUND:

ABCG2 protein overexpression and FLT3 internal tandem duplication (ITD) correlate with higher relapse rate and shorter disease‐free survival (DFS) in acute myeloid leukemia (AML), but no data are available on the possible effect of concomitant presence of these 2 factors.

METHODS:

The authors analyzed the outcome of 166 cases of adult AML patients who were homogeneously treated with a fludarabine‐based induction therapy.

RESULTS:

ABCG2 overexpression and FLT3‐ITD were detected in 83 (50%) and 47 (28%) patients, respectively. A significant correlation was found between ABCG2 positivity and FLT3 mutation, with 33 (40%) ITD in 83 ABCG2‐positive patients compared with 14 (17%) ITD in 83 ABCG2‐negative patients (P = .002). Complete remission (CR) after induction therapy was achieved in 95 (57%) patients. Neither ABCG2 overexpression nor FLT3‐ITD had any impact on achievement of CR. Relapse occurred in 42 of 95 (44%) patients at a median time of 28 months. Time to relapse was shortened in patients overexpressing ABCG2 (P = .0004). DFS was not affected by FLT3‐ITD alone, but FLT3 mutation significantly worsened long‐term outcome of ABCG2‐positive patients. DFS at 1 and 3 years in patients with overexpression of both ABCG2 and FLT3‐ITD was only 36% and 28%, respectively; in ABCG2‐positive/FLT3‐negative patients, DFS at 1 and 3 years was 65% and 48%, respectively; and in ABCG2‐negative cases (regardless of FLT3 status), DFS at 1 and 3 years was greater than 85% and 75%.

CONCLUSIONS:

Concomitant overexpression of ABCG2 and FLT3‐ITD is relatively frequent and identifies a subgroup of AML patients with a significantly worse prognosis. The possible interactions between these 2 prognostic factors need to be defined. Cancer 2011. © 2010 American Cancer Society.
Clinicopathologic factors of the recurrent tumor predict outcome in patients with ipsilateral breast tumor recurrence
Authors: Panet‐Raymond Valerie , Truong Pauline T. , Alexander Cheryl , Lesperance Mary , McDonald Rachel E. , Watson Peter H.
Published: November 2010

BACKGROUND:

The role of clinicopathologic characteristics of the recurrent tumor in determining survival in a cohort of patients with ipsilateral breast tumor recurrence (IBTR) was investigated.

METHODS:

Among 6020 women with pT1‐T2, pN0‐1, M0 treated with breast‐conserving surgery from 1989 to 1999, 269 developed isolated IBTR. Ten‐year Kaplan‐Meier breast cancer‐specific survival (BCSS) and overall survival (OS), calculated from date of IBTR, were analyzed according to clinicopathologic characteristics.

RESULTS:

Factors that were associated with diminished OS and BCSS on univariate analysis were: time to IBTR ≤48 months, lymphovascular invasion positive status, estrogen receptor (ER) negative status, high grade, clinical IBTR detection, biopsy alone, and close/positive margins (all P < .05). On multivariate analysis, time to IBTR ≤48 months (hazard ratio [HR], 1.87, P = .012), lymphovascular invasion positive status (HR, 2.46; P < .001), ER negative status (HR, 2.08; P = .013), high‐grade recurrent disease (HR, 1.88; P = .013), and close/positive margins after surgery for IBTR (HR, 1.94; P = .013) retained significance for prediction of diminished OS. When stratified according to number of adverse prognostic features, 10‐year OS was 70.4% in patients with 1 factor, 35.8% with 2 factors, and 19.9% with 3 or more factors (P < .001).

CONCLUSIONS:

Time to recurrence ≤48 months, lymphovascular invasion positive status, ER negative status, high‐grade histology, and close/positive margins in association with the recurrent tumor are independent prognostic factors for survival after IBTR. The presence of 2 or more of these features at recurrence is significantly associated with poor OS. These criteria can be used to prognosticate and guide clinical decisions after recurrence. Cancer 2011. © 2010 American Cancer Society.
Lysyl oxidase: A lung adenocarcinoma biomarker of invasion and survival
Authors: Wilgus May‐Lin , Borczuk Alain C. , Stoopler Mark , Ginsburg Mark , Gorenstein Lyall , Sonett Joshua R. , Powell Charles A.
Published: November 2010

BACKGROUND:

Lung adenocarcinoma invasion and metastasis arises from autocrine and paracrine signaling events between tumor epithelial cells and the stromal microenvironment that is mediated in part by transforming growth factor‐β (TGF‐β) signaling. The copper‐dependent amine oxidase lysyl oxidase (LOX) plays a role in extracellular matrix structure and is up‐regulated in invasive type II TGF‐β receptor‐deficient cells. The authors hypothesized that LOX expression is associated with extent of invasion and survival in patients with lung adenocarcinoma.

METHODS:

LOX immunohistochemical staining was examined in 166 surgically resected lung adenocarcinomas and results were correlated with clinicopathological features and survival.

RESULTS:

High‐intensity LOX staining was found to be associated with the linear extent of invasion (Spearman correlation coefficient = 0.2; P = .01). There was an association between high LOX staining and decreased 5‐year survival observed within the entire cohort (log‐rank P < .001) and among the patients with stage I disease (n = 119; P < .001). Cox proportional hazards regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5‐year mortality for all patients (hazard ratio [HR], 2.55; 95% confidence interval [95% CI], 1.51‐4.30 [P < .001]) and for patients with Stage I disease (HR, 3.51; 95% CI, 1.77‐6.99 [P < .001]). LOX expression was found to be independently associated with risk of death after adjustment for relevant covariates (HR, 2.29; 95% CI, 1.33‐3.94 [P = .003]).

CONCLUSIONS:

Higher expression of LOX is associated with invasion and is an independent predictor of poor prognosis in patients with early stage lung adenocarcinoma. Cancer 2011. © 2010 American Cancer Society.
Genomic differences between estrogen receptor (ER)‐positive and ER‐negative human breast carcinoma identified by single nucleotide polymorphism array comparative genome hybridization analysis
Authors: Fang Min , Toher Jessica , Morgan Martin , Davison Jerry , Tannenbaum Susan , Claffey Kevin
Published: November 2010

BACKGROUND:

Estrogen receptor (ER) remains one of the most important biomarkers for breast cancer subtyping and prognosis, and comparative genome hybridization has greatly contributed to the understanding of global genetic imbalance. The authors used single‐nucleotide polymorphism (SNP) arrays to compare overall copy number aberrations (CNAs) as well as loss of heterozygosity (LOH) of the entire human genome in ER‐positive and ER‐negative breast carcinomas.

METHODS:

DNA was extracted from frozen tumor sections of 21 breast carcinoma specimens and analyzed with a proprietary 50K XbaI SNP array. Copy number and LOH probability values were derived for each sample. Data were analyzed using bioinformatics and computational software, and permutation tests were used to estimate the significance of these values.

RESULTS:

There was a global increase in CNAs and LOH in ER‐negative relative to ER‐positive cancers. Gain of the long arm of chromosome 1 (1q) and 8q were the most obvious changes common in both subtypes: An increase in the chromosome 1 short arm (1p)/1q ratio was observed in ER‐negative samples, and an increased 16p/16q ratio was observed in ER‐positive samples. Significant CNAs (adjusted P<.05) in ER‐negative relative to ER‐positive tumors included 5q deletion, loss of 15q, and gain of 2p and 21q. Copy‐neutral LOH (cnLOH) common to both ER‐positive and ER‐negative samples included 9p21, the p16 tumor suppressor locus, and 4q13, the RCHY1 (ring finger and CHY zinc finger domain‐containing 1) oncogene locus. Of particular interest was an enrichment of 17q LOH among the ER‐negative tumors, potentially suggesting breast cancer 1 gene (BRCA1) mutations.

CONCLUSIONS:

SNP array detected both genetic imbalances and cnLOH and was capable of discriminating ER‐negative breast cancer from ER‐positive breast cancer. Cancer 2011. © 2010 American Cancer Society.
Arrival times for the wave equation
Authors: McLaughlin Joyce R. , Yoon Jeong‐Rock
Published: November 2010

We establish a definition of arrival time of a wavefront for a propagating wave in anisotropic media that is initially at rest and where the governing partial differential equation is the anisotropic wave equation. This definition of arrival time is not the same as the one in [8, 12]; it eliminates pathological discontinuities that can occur with the older definition and is still consistent with physical intuition. What is substantively new here is that we show that the newly defined arrival time is locally Lipschitz‐continuous. Then following the method in [8, 12] we establish that it satisfies the eikonal equation. Furthermore, in the isotropic case we establish that the arrival time, as defined here, is the unique viscosity solution of the eikonal equation. Our motivation for this work is to use this arrival time at points in the interior of a physical or biological material, which is estimated from displacement measurements, to determine properties of the medium that are represented as functions in the eikonal equation; see [8, 10, 11, 12]. © 2010 Wiley Periodicals, Inc.
Aluminophosphates for CO2 Separation
Authors: Liu Qingling , Cheung Ngo Chuen Ocean , Garcia‐Bennett Alfonso E. , Hedin Niklas
Published: November 2010

The pressure‐swing adsorption method for carbon dioxide capture would ideally be facilitated by adsorbents with a high capacity and a high selectivity for CO2. Several aluminophosphates with 8‐ring window apertures (AlPO4‐17, AlPO4‐18, AlPO4‐53, and AlPO4‐25) were synthesized by hydrothermal crystallization, calcined, and their CO2 uptake and CO2/N2 selectivity were studied. CO2 and N2 uptake was determined for pressures up to 101 kPa at 273 and 293 K. Langmuir and Toth adsorption models were used to describe the adsorption isotherms. The CO2 and N2 uptakes strongly indicated that the squeezed 8‐ring windows of certain aluminophosphates can sieve CO2 from a CO2 and N2 gas mixture. Both AlPO4‐53 and AlPO4‐25 exhibited a remarkably higher uptake of CO2 compared to N2. The hydrophilicity of the AlPO4 materials was investigated by means of water adsorption, and the results showed that all of the tested aluminophosphates were less water sensitive than a benchmark zeolite (13X). In particular, AlPO4‐53 and AlPO4‐25 showed a very low degree of water uptake with up to 20–30 % relative humidity. Determination of cyclic adsorption and desorption confirmed the relatively hydrophobic nature of the aluminophosphates, which render them less energy costly for the regeneration of adsorbents.
Sox11 regulates survival and axonal growth of embryonic sensory neurons
Authors: Lin L. , Lee V.M. , Wang Y. , Lin J.S. , Sock E. , Wegner M. , Lei L.
Published: November 2010

Sensory neurons transduce various stimuli including temperature, pain, and touch from the periphery to the central nervous system. Sensory neuron development is governed by a combination of extracellular cues and specific gene expression. We demonstrated that the transcription factor Sox11 was highly expressed in the developing sensory neurons. To test the function of Sox11, we used a knockin mouse model where the entire coding region of Sox11 was replaced by a LacZ reporter. The ablation of Sox11 caused severe reduction in sensory neuron survival in the trigeminal and dorsal root ganglia, although it did not affect migration of neural crest cells or acquisition of major sensory neuron subtypes. We further demonstrated that ablating Sox11 caused an arrest of axonal outgrowth in vivo and in vitro. This defect could not be fully rescued by blocking cell death. Our data suggest that Sox11 is a key regulator of sensory neuron development. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Generation of a non‐leaky heat shock–inducible Cre line for conditional Cre/lox strategies in zebrafish
Authors: Hans Stefan , Freudenreich Dorian , Geffarth Michaela , Kaslin Jan , Machate Anja , Brand Michael
Published: November 2010

Cre‐mediated site‐specific recombination has emerged as an indispensable tool for the precise manipulation of the mammalian genome. Recently, we showed that Cre is also highly efficient in zebrafish and temporal control of recombination can be achieved by using the ligand‐inducible CreERT2. Previous attempts have been made to control recombination by using the temperature inducible hsp70l promoter to conditionally drive the expression of Cre or EGFP‐Cre, respectively. However, in this study we demonstrate that the hsp70l promoter possesses a basal leakiness resulting in Cre‐mediated recombination even at permissive temperatures. In order to prevent non‐conditional recombination, we combined the hsp70l promoter with a mCherry‐tagged ligand‐inducible CreERT2. At permissive temperatures and in the absence of the ligand tamoxifen (TAM), no non‐conditional recombination is observed indicating tight regulation of CreERT2. Instead, comprehensive site‐specific recombination is mediated following heat induction and administration of TAM. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
A basic study of optimal investment of power sources considering environmental measures: Economic evaluation of CCS through a real options approach
Authors: Kato Moritoshi , Zhou Yicheng
Published: November 2010

This paper proposes a novel method based on real options theory for economic evaluation of the replacement of an old coal‐fired thermal power plant (COAL) with a coal‐fired thermal power plant that includes a CCS (carbon dioxide capture and storage) unit. We calculate the real option value (ROV) of CCS as the value of an American call option with dividend, treating the increased carbon cost of COAL due to the delay of replacement as opportunity cost. The appropriate construction time of a CCS unit is evaluated by binominal decision tree analysis for option exercise. We calculate the change of project ROV and the appropriate construction time according to the difference in carbon emission benchmarks and the variation of the maintenance cost of COAL. The effect of power station lifetime is also analyzed. We conclude that flexibility in the timing of decision making increases the value of a project. We also found that CCS is an economically justifiable technology option under forthcoming restrictions on carbon emissions. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 174(3): 9–17, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/eej.21065
Borrelia species induce inflammasome activation and IL‐17 production through a caspase‐1‐dependent mechanism
Authors: Oosting Marije , van de Veerdonk Frank L. , Kanneganti Thirumala‐Devi , Sturm Patrick , Verschueren Ineke , Berende Anneleen , van der Meer Jos W. M. , Kullberg Bart‐Jan , Netea Mihai G. , Joosten Leo A. B.
Published: November 2010

Borrelia burgdorferi spirochetes cause Lyme disease, which can result in severe clinical symptoms such as multiple joint inflammation and neurological disorders. IFN‐γ and IL‐17 have been suggested to play an important role in the host defense against Borrelia, and in the immunopathology of Lyme disease. The caspase‐1‐dependent cytokine IL‐1β has been linked to the generation of IL‐17‐producing T cells, whereas caspase‐1‐mediated IL‐18 is crucial for IFN‐γ production. In this study, we show by using knockout mice the role of inflammasome‐activated caspase‐1 in the regulation of cytokine responses by B. burgdorferi. Caspase‐1‐deficient cells showed significantly less IFN‐γ and IL‐17 production after Borrelia stimulation. A lack of IL‐1β was responsible for the defective IL‐17 production, whereas IL‐18 was crucial for the IFN‐γ production. Caspase‐1‐dependent IL‐33 played no role in the Borrelia‐induced production of IL‐1β, IFN‐γ or IL‐17. In conclusion, we describe for the first time the role of the inflammasome‐dependent caspase‐1 activation of cytokines in the regulation of IL‐17 production induced by Borrelia spp. As IL‐17 has been implicated in the pathogenesis of chronic Lyme disease, these data suggest that caspase‐1 targeting may represent a new immunomodulatory strategy for the treatment of complications of late stage Lyme disease.
Threshold levels of Flt3‐ligand are required for the generation and survival of lymphoid progenitors and B‐cell precursors
Authors: Dolence Joseph J. , Gwin Kimberly , Frank Elena , Medina Kay L.
Published: November 2010

The generation of B‐cell precursors (BCP) from lymphohematopoietic progenitors (LHP) in bone marrow is dependent on signals provided by the receptor tyrosine kinase Flt3 and its ligand, Flt3‐ligand (FL). Mice deficient in FL exhibit striking reductions in LHP and BCP. Currently, the mechanism by which Flt3 regulates lymphoid lineage/B‐cell development is unknown. Here, we show that haploinsufficiency of FL (FL+/−) reduced the numbers of LHP, common lymphoid progenitors, and pro‐B cells, suggesting that FL levels set a threshold for B lymphopoiesis. Limiting dilution analysis confirmed reduced BCP frequency in FL+/− mice. Real‐time PCR of LHP from FL+/− animals showed increased transcripts of the B lineage inhibitor id1. However, targeted deletion of id1 did not restore the lymphoid/B lineage deficiencies in FL−/− mice, supporting Id1‐independent mechanisms. BrdU incorporation studies established that FL is not essential for the proliferation of Flt3+ multipotential progenitors. Analysis of FL−/− progenitors expressing low levels of Flt3 revealed decreased levels of the pro‐survival factor Mcl1. Consequently, the Flt3+ LHP progeny of Flt3low LSK+ cells exhibited increased Annexin V staining. Together, these data suggest that Flt3 signaling initiates a cascade of events in Flt3low precursors that promote the survival of LHP from which BCP are derived.
Synthesis and Structural Characterization of New Chiral (Biscarbene)platinum(II) Complexes
Authors: Riederer Stephanie K. U. , Bechlars Bettina , Herrmann Wolfgang A. , Kühn Fritz E.
Published: November 2010

New chiral bis(triazolium) salts have been prepared in good yields. The corresponding mononuclear platinum(II) complexes [Pt{bis(NHC)}X2] (X = Br, I) have been synthesized and spectroscopically characterized. One of the synthesized biscarbene complexes has also been characterised by X‐ray crystallography. These complexes are efficient catalyst precursors for the hydrosilylation of 1‐octene.
Ultra high performance liquid chromatography–mass spectrometric analysis of oxidized free fatty acids and acylglycerols
Authors: Tarvainen Marko , Suomela Jukka‐Pekka , Kallio Heikki
Published: November 2010

A fast ultra high performance liquid chromatography (UHPLC)–electrospray ionization (ESI)–mass spectrometric (MS) method was developed for simultaneous analysis of free fatty acids (FFAs), monoacylglycerols (MAG), diacylglycerols (DAG), triacylglycerols (TAG), and their oxidized equivalents. Effect of elevated column temperature was studied in order to optimize the chromatography of closely eluting peaks and to reduce high back pressure formed in UHPLC. The elevated temperature enabled high flow rate, better mass transfer, and therefore more narrow peaks and better separation of the analytes. The new method was applied to the analysis of total lipid extracts of lipolysis samples prepared by an artificial digestion model in order to investigate oxidized lipids and changes in their profiles in the chyme. Over 150 compounds were identified from the extracts. The UHPLC–ESI–MS method was proved to be fast, highly selective, and sensitive. Compared to a previously used high performance LC–ESI–MS method, the new UHPLC–ESI–MS method was over five times faster and consumed one tenth of the solvents while producing comparable quantitative results.

Practical applications: Edible oils and fats contain mainly TAGs, the lipolysis of which produces FFAs and MAGs with minor DAG components. These compounds are susceptible to oxidation in the stomach, and therefore the analysis of the oxidation products is important. Fast determination of FFAs and acylglycerols is also important in quality control of biodiesel. Our new method enables accurate and sensitive determination of different molecular species present in digested and processed samples with minimal sample preparation requirements. In this respect, the new method is applicable to large scale and fast screening of biological samples for lipidomic and metabolomic studies.
Integration profile of retroviral vector in gene therapy treated patients is cell‐specific according to gene expression and chromatin conformation of target cell
Authors: Biasco Luca , Ambrosi Alessandro , Pellin Danilo , Bartholomae Cynthia , Brigida Immacolata , Roncarolo Maria Grazia , Di Serio Clelia , von Kalle Christof , Schmidt Manfred , Aiuti Alessandro
Published: November 2010

The analysis of genomic distribution of retroviral vectors is a powerful tool to monitor ‘vector‐on‐host’ effects in gene therapy (GT) trials but also provides crucial information about ‘host‐on‐vector’ influences based on the target cell genetic and epigenetic state. We had the unique occasion to compare the insertional profile of the same therapeutic moloney murine leukemia virus (MLV) vector in the context of the adenosine deaminase‐severe combined immunodeficiency (ADA‐SCID) genetic background in two GT trials based on infusions of transduced mature lymphocytes (peripheral blood lymphocytes, PBL) or a single infusion of haematopoietic stem/progenitor cells (HSC). We found that vector insertions are cell‐specific according to the differential expression profile of target cells, favouring, in PBL‐GT, genes involved in immune system and T‐cell functions/pathways as well as T‐cell DNase hypersensitive sites, differently from HSC‐GT. Chromatin conformations and histone modifications influenced integration preferences but we discovered that only H3K27me3 was cell‐specifically disfavoured, thus representing a key epigenetic determinant of cell‐type dependent insertion distribution. Our study shows that MLV vector insertional profile is cell‐specific according to the genetic/chromatin state of the target cell both in vitro and in vivo in patients several years after GT.

See accompanying Closeup by Baum DOI: http://dx.doi.org/10.1002/emmm.201000110.
Persistent resource allocations for VoIP traffic in packet‐switching mobile cellular networks
Authors: Sambale K. , Klagges K. , Rad R. Rezai
Published: November 2010

It is expected that future IMT‐Advanced systems will operate packet‐switched due to the dominance of data services. However, it is inherent to packet‐switched systems to not cope well with voice services as periodic resource usage patterns are not signalled efficiently. In this paper, we present a simple technique to reduce the signalling overhead for resource allocations especially for voice‐over‐IP (VoIP) traffic thus increasing the VoIP capacity of the system, considerably. The proposed technique assigns persistent resource allocation (PRA) per VoIP connection that are valid for a fix number of frames. Resource allocations for succeeding frames have to be signalled by new PRAs. This supersedes any procedures for deallocation of PRAs and associated error handling. Within our work we introduce an analytical model to evaluate the possible VoIP capacity gains. Additionally, we show results of event‐driven simulations to validate the analysis. The PRA technique is applicable to all packet‐switched systems. We show exemplary results for the WiMAX system. In this paper, we present a simple technique called persistent resource allocation (PRA) to reduce the signalling overhead in packet‐switching mobile radio networks, especially for VoIP traffic. The figure shows our idea: resource allocations for mobile station (MS) 42 are signalled in frame n (solid lines) and remain valid in frame $n + k$ up to frame $n + (m{-} 1)k$ (dashed lines). The parameter k matches the period length of packet arrival in number of frames and m limits the life time (time‐to‐live) of the PRA. Copyright © 2010 John Wiley & Sons, Ltd.
High‐resolution genomic screening in mantle cell lymphoma—specific changes correlate with genomic complexity, the proliferation signature and survival
Authors: Halldórsdóttir Anna M. , Sander Birgitta , Göransson Hanna , Isaksson Anders , Kimby Eva , Mansouri Mahmoud , Rosenquist Richard , Ehrencrona Hans
Published: November 2010

Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) and numerous copy number aberrations (CNAs). Recently, gene expression profiling defined a proliferation gene expression signature in MCL where high scores predict shorter survival. We investigated 31 MCL cases using high‐density single nucleotide polymorphism arrays and correlated CNA patterns with the proliferation signature and with clinical data. Many recurrent CNAs typical of MCL were detected, including losses at 1p (55%), 8p (29%), 9q (29%), 11q (55%), 13q (42%) and 17p (32%), and gains at 3q (39%), 8q (26%), 15q (23%) and 18q (23%). A novel deleted region at 20q (16%) contained only one candidate gene, ZFP64, a putative tumor suppressor. Unsupervised clustering identified subgroups with different patterns of CNAs, including a subset (19%) characterized by the presence of 11q loss in all cases and by the absence of 13q loss, and 3q and 7p gains. Losses at 1p, 8p, 13q and 17p were associated with increased genomic complexity. High proliferation signature scores correlated with increased number of large (>15 Mbp) CNAs (P = 0.03) as well as copy number gains at 7p (P = 0.02) and losses at 9q (P = 0.04). Furthermore, large/complex 13q losses were associated with improved survival (P < 0.05) as were losses/copy number neutral LOH at 19p13 (P = 0.01). In summary, this high‐resolution genomic analysis identified novel aberrations and revealed that several CNAs correlated with genomic complexity, the proliferation status and survival. © 2010 Wiley‐Liss,Inc.
Multiplexed immunobead‐based profiling of cytokine markers for detection of nasopharyngeal carcinoma and prognosis of patient survival
Authors: Chang Kai‐Ping , Chang Ya‐Ting , Wu Chih‐Ching , Liu Yu‐Ling , Chen Min‐Chi , Tsang Ngan‐Ming , Hsu Cheng‐Lung , Chang Yu‐Sun , Yu Jau‐Song
Published: November 2010

Background

The purpose of this study was to examine cytokine profiles of peripheral blood for nasopharyngeal carcinoma (NPC).

Methods

A total of 132 patients with untreated NPC, 169 healthy individuals, and 32 patients with chronic rhinosinusitis (CRS) were enrolled in this study. The plasma levels of 13 cytokines were measured by the multiplexed immunobead‐based method.

Results

The levels of interleukin (IL)‐6, IL‐8, interferon‐inducible protein 10 (IP‐10), tumor necrosis factor (TNF)‐α, vascular endothelial growth factor (VEGF), and macrophage inflammatory protein (MIP)‐3α were significantly elevated in patients with NPC; but the stem cell factor (SCF) levels were significantly lower. The levels of IL‐6, IL‐8, IP‐10, and MIP‐3α were significantly elevated in patients with advanced stages disease and correlated with Epstein–Barr virus (EBV) DNA. A 2‐marker panel consisting of MIP‐3α and SCF increased the screening efficacy of EBV‐specific viral capsid antigen (VCA) IgA or EBV DNA, although the addition of MIP‐3α and SCF to the combined set of currently available markers (EBV VCA IgA and EBV DNA) did not improve the accuracy of the diagnostic panel. The patients with NPC with higher levels of IL‐8, VEGF, MIP‐3α, and EBV DNA had worse prognoses for overall survival (p = .008, .035, .005, and .007, respectively).

Conclusion

Simultaneous, large‐scale measurement of multiple cytokines may improve NPC detection and prognostic prediction. © 2010 Wiley Periodicals, Inc. Head Neck, 2011