bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative Coupling Reactions of 1,3‐Diarylpropene Derivatives to Dibenzo[a,c]cycloheptenes by PIFA
Authors: Hackelöer Kristina , Schnakenburg Gregor , Waldvogel Siegfried R. 
Published: September 2011

AbstractThe oxidative cyclization reactions of a variety of α‐benzylcinnamates can be selectively performed with hypervalent iodine as an oxidant. The dibenzo[a,c]cycloheptenes were isolated in up to 55 % yield. When an oxo substrate is applied, the yield was significantly increased. With this synthetic approach, a central intermediate for the synthesis of metasequirin‐B was obtained in three steps from very simple starting materials. For this transformation, both aryl moieties have to be activated.
Zur Dimensionierung von Nagelwänden
Authors: Renk Daniel , Kolymbas Dimitrios 
Published: September 2011

AbstractNagelwände sind Verbundkörper aus Boden und Stahlstäben und können als Gewichts‐Stützmauern den Erddruck aufnehmen. Ihre Standsicherheit wird aufgrund von Starrkörperbruchmechanismen unter Berücksichtigung von Nagelzugkräften nachgewiesen, wobei Gleitfuge und Nägel in etwa senkrecht zueinander stehen. Die dadurch bedingte Kinematik vermag jedoch kaum, Zugkräfte in den Nägeln zu mobilisieren, was einen Widerspruch darstellt. Bei dem hier vorgeschlagenen Nachweis werden Spannungen im Verbundkörper betrachtet, wodurch dieser Widerspruch behoben wird.On the design of nailed retaining wallsNailed retaining walls are composites consisting of soil and steel rods. They act as retaining walls and resist earth pressure. Usual design methods are based on the consideration of rigid block failure mechanisms, where the shear band and the nails intersect at nearly 90°. However, this mechanism cannot mobilize tensile forces in the nails, what is contradictory to the assumption of the existing methods. We propose a new design‐method which is based on the consideration of stress within the composite and, thus, removes the afore mentioned contradiction.
Explicit modeling of cone and strip footing penetration under drained and undrained conditions using a visco‐hypoplastic model
Authors: Qiu Gang , Grabe Jürgen 
Published: September 2011

AbstractIn this paper a visco‐hypoplastic model, which can describe viscous behavior including creep, relaxation and rate dependency of cohesive soils, is implemented in the form of a user subroutine VUMAT in Abaqus/Explicit to model soil‐structure interaction in clayey soil. The VUMAT subroutine is verified with a UMAT subroutine by back‐calculating standard element tests. In addition, an uncoupled analysis strategy, using effective parameters to calculate the stresses in nearly incompressible materials, is implemented in user subroutines to model the soil under undrained conditions. A strategy of scaling the reference creep rate is used to improve the efficiency of the explicit analyses. Furthermore, the penetration process of a cone penetration test (CPT) in a cohesive soil is simulated to investigate the effects of penetration velocity on the cone penetration resistance. Finally, the user subroutine VUMAT is used together with the coupled Eulerian‐Lagrangian method to investigate a strip footing problem.Explizite Modellierung des Eindringens einer Sonde und eines Streifenfundaments unter dränierten und undränierten Bedingungen mittels eines visko‐hypoplastischen StoffgesetzesIn diesem Artikel wird ein visko‐hypoplastisches Modell vorgestellt, welches das viskose Verhalten einschließlich Kriechen, Relaxation und Viskosität eines bindigen Bodens beschreiben kann. Dieses Modell wird in der Form einer “user Subroutine” VUMAT in Abaqus/Explicit implementiert, damit die Anwendungen der CEL‐Methode zur Simulation der Ton‐Struktur‐Interaktion erweitert werden können. Die VUMAT‐Routine wird mithilfe der UMAT‐Routine durch Nachrechnung von Elementversuchen überprüft. Zusätzlich wird eine entkoppelte Analysestrategie in die VUMAT‐Routine implementiert, um eine Modellierung des Bodens unter undränierten Bedingungen zu ermöglichen. Durch Skalierung der Referenzkriechrate wird die Effizienz der expliziten Analysen verbessert. Danach wird der Penetrationsvorgang einer Drucksonde in bindigen Böden mithilfe der FE‐Modellierung simuliert, um den Einfluss der Eindringgeschwindigkeit auf den Drucksondierwiderstand zu untersuchen. Schließlich wird mit dem Eindrücken eines Streifenfundaments in den Untergrund ein komplexes geotechnisches Randwertproblem mit Verwendung der gekoppelten Euler‐Lagrange‐Methode mit der VUMATRoutine untersucht.
Zur Gleitkreisberechnung ohne Lamellen nach DIN 4084
Authors: Goldscheider Michael , Hettler Achim 
Published: September 2011

AbstractMit den in DIN 4084:2009‐01 angegebenen Formeln zur Berechnung von Gleitkreisen ohne Lamelleneinteilung, die auf Fröhlich zurückgehen, wird der sogenannte Ausnutzungsgrad der Bemessungswiderstände nicht in Übereinstimmung mit seiner Definition erhalten. In diesem Beitrag wird ein statisch korrektes und den heutigen Sicherheitsdefinitionen entsprechendes Berechnungsverfahren vorgestellt. Es beruht auf den elementaren Grundlagen der Statik starrer Scheiben. Wie allgemein bei gekrümmten Gleitlinien sind statische Annahmen notwendig; diese werden begründet und sind nicht stärker als beim Lamellenverfahren. Wie beim Lamellenverfahren ist im Allgemeinen eine Iteration erforderlich. Die Methode wird auch auf verankerte Böschungen erweitert. Hierbei kann man wahlweise ohne Iteration die erforderliche Ankerkraft oder mit Iteration den Ausnutzungsgrad bei gewählter Ankerkraft bestimmen. Die Methode lässt sich zeichnerisch nach den Regeln der grafischen Statik oder rein rechnerisch mit Handrechnung durchführen. Die rechnerische Methode eignet sich auch für ein Computerprogramm. Die Anwendung wird am Beispiel einer verankerten Baugrubenböschung ausführlich vorgeführt.Slip circle stability calculation without slices based on DIN 4084Using the formulas represented in DIN 4084:2009‐01 and adopted from Fröhlich to calculate slip circle stability without slices the so‐called degree of utilization of the design values of resistances is not obtained in accordance with its present definition. In this paper, a statically correct method of calculation corresponding to the current safety definitions is outlined. It is deduced from the principles of statics of rigid bodies. As generally for circular slip lines some statical assumptions must be introduced; those are explained and are not more restrictive than in the case of the slice methods. As for the slice methods, iteration is necessary, in general, to solve the equations. The method is extended for the problem of anchored slopes. Optionally, the required anchor force can be determined without iteration or the degree of utilization can be obtained for a given anchor force with iteration. The method can be performed graphically taking into account the rules of graphical statics or analytically by short basic calculation. The analytical algorithm also is compatible with computer programming. The application is demonstrated by an example of an anchored excavation slope.
A MARKOV MODEL TO ESTIMATE SALMONELLA MORBIDITY, MORTALITY, ILLNESS DURATION, AND COST
Authors: Herrick Robert L. , Buchberger Steven G. , Clark Robert M. , Kupferle Margaret , Murray Regan , Succop Paul 
Published: September 2011

ABSTRACTApproximately 690 000–1 790 000 Salmonella cases, 20 000 hospitalizations, and 400 deaths occur in the USA annually, costing approximately $2.6bn. Existing models estimate morbidity, mortality, and cost solely from incidence. They do not estimate illness duration or use time as an independent cost predictor. Existing models may underestimate physician visits, hospitalizations, deaths, and associated costs. We developed a Markov chain Monte Carlo model to estimate illness duration, physician/emergency room visits, inpatient hospitalizations, mortality, and resultant costs for a given Salmonella incidence. Interested parties include society, third‐party payers, health providers, federal, state and local governments, businesses, and individual patients and their families. The marginal approach estimates individual disease behavior for every patient, explicitly estimates disease duration and calculates separate time‐dependent costs. The aggregate approach is a Markov equivalent of the existing models; it assumes average disease behavior and cost for a given morbidity/mortality. Transition probabilities were drawn from a meta‐analysis of 53 Salmonella studies. Both approaches were tested using the 1993 Salmonella typhimurium outbreak in Gideon, Missouri. This protocol can be applied to estimate morbidity, mortality and cost of specific outbreaks, provide better national Salmonella burden estimates, and estimate the benefits of reducing Salmonella risk. Copyright © 2011 John Wiley & Sons, Ltd.
Serum ferritin concentration and transferrin saturation before liver transplantation predict decreased long-term recipient survival
Authors: Weismüller Tobias J. , Kirchner Gabriele I. , Scherer Marcus N. , Negm Ahmed A. , Schnitzbauer Andreas A. , Lehner Frank , Klempnauer Jürgen , Schlitt Hans J. , Manns Michael P. , Strassburg Christian P. 
Published: September 2011

Abstract

Serum ferritin (SF) concentration is a widely available parameter used to assess iron homeostasis. It has been described as a marker to identify high-risk patients awaiting liver transplantation (LT) but is also elevated in systemic immune-mediated diseases, metabolic syndrome, and in hemodialysis where it is associated with an inferior prognosis. This study analyzed whether SF is not only a predictor of liver-related mortality prior to LT but also an independent marker of survival following LT. In a dual-center, retrospective study, a cohort of 328 consecutive first-LT patients from Hannover Medical School, Germany (2003-2008, follow-up 1260 days), and 82 consecutive LT patients from Regensburg University Hospital, Germany (2003-2007, follow-up 1355 days) as validation cohort were analyzed. In patients exhibiting SF ≥365 μg/L versus <365 μg/L prior to LT, 1-, 3-, and 5-year post-LT survival was 73.3% versus 81.1%, 64.4% versus 77.3%, and 61.1% versus 74.4%, respectively (overall survival

P

= 0.0097), which was confirmed in the validation cohort (overall survival of 55% versus 83.3%,

P

= 0.005). Multivariate analyses identified SF ≥365 μg/L combined with transferrin saturation (TFS) <55%, hepatocellular carcinoma, and the survival after LT (SALT) score as independent risk factors for death. In patients with SF concentrations ≥365 μg/L and TFS <55%, overall survival was 54% versus 74.8% in the remaining group (

P

= 0.003). In the validation cohort, it was 28.6% versus 72% (

P

= 0.017), respectively.

Conclusion:

SF concentration ≥365 μg/L in combination with TFS <55% before LT is an independent risk factor for mortality following LT. Lower TFS combined with elevated SF concentrations indicate that acute phase mechanisms beyond iron overload may play a prognostic role. SF concentration therefore not only predicts pre-LT mortality but also death following LT. (Hepatology 2011;)
Indeterminate 1-2-cm nodules found on hepatocellular carcinoma surveillance: Biopsy for all, some, or none?
Authors: Khalili Korosh , Kim Tae Kyoung , Jang Hyun-Jung , Yazdi Leyla Kochak , Guindi Maha , Sherman Morris 
Published: September 2011

Abstract

In the latest hepatocellular carcinoma (HCC) management guidelines by the American Association for the Study of Liver Diseases, biopsy is advocated for all nodules deemed indeterminate after imaging work-up by contrast-enhanced scans. However, the latest guidelines' imaging work-up algorithm has been shown to improve sensitivity of characterization of HCC for 1-2-cm nodules, decreasing the proportion of HCCs that remain indeterminate after imaging work-up. We undertook a study of 1-2-cm indeterminate nodules to determine what proportions are malignant and which variables can be used to limit biopsy to a subset of nodules at higher risk of malignancy. Eighty consecutive patients with 93 indeterminate nodules were included. Final diagnosis was established in 85 nodules, with 13 malignant (9 by biopsy, 4 by growth) and 72 benign (stability of ≥18 months). Cause of liver disease, ethnicity, size, arterial hypervascularity, venous hypoenhancement, and presence of synchronous typical HCC were analyzed by univariate logistic analysis to determine significant predictors of malignancy. Rate of malignancy among indeterminate 1-2-cm nodules was found to be 14%-23%. Only arterial hypervascularity [odds ratio (OR), 3.7) and presence of synchronous HCC (OR, 7.1) were significant predictors of malignancy. A strategy of limiting biopsy to nodules that had either feature would result in 23 biopsies and potentially detect 8 of 13 malignant nodules, yielding a sensitivity of 62% and specificity of 79%.

Conclusion:

The prevalence of malignancy among 1-2-cm indeterminate nodules is low (14%-23%), and biopsy of all such nodules results in many negative results. Limiting biopsy to nodules with arterial hypervascularity or in the presence of a synchronous typical HCC would detect the majority of HCCs while substantially reducing the number of biopsies. (Hepatology 2011)
Tenascin-C: A novel mediator of hepatic ischemia and reperfusion injury
Authors: Kuriyama Naohisa , Duarte Sergio , Hamada Takashi , Busuttil Ronald W. , Coito Ana J. 
Published: September 2011

Abstract

Hepatic ischemia/reperfusion (IRI) injury remains a major challenge in clinical orthotopic liver transplantation (OLT). Tenascin-C (Tnc) is an extracellular matrix protein (ECM) involved in various aspects of immunity and tissue injury. Using a Tnc-deficient mouse model, we present data that suggest an active role for Tnc in liver IRI. We show that Tnc-deficient mice have a reduction in liver damage and a significant improvement in liver regeneration after IRI. The inability of Tnc−/− mice to express Tnc significantly reduced the levels of active caspase-3/transferase-mediated dUTP nick end-labeling (TUNEL) apoptotic markers and enhanced the expression of the proliferation cell nuclear antigen (PCNA) after liver IRI. The lack of Tnc expression resulted in impaired leukocyte recruitment and decreased expressions of interleukin (IL)-1β, IL-6, and CXCL2 after liver reperfusion. Tnc-deficient livers were characterized by altered expression patterns of vascular adhesion molecules, such as vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 post-IRI. Moreover, matrix metalloproteinase-9 (MMP-9) synthesis, which facilitates leukocyte transmigration across vascular barriers in liver IRI, was markedly down-regulated in the absence of Tnc. We also show that Tnc is capable of inducing MMP-9 expression in isolated neutrophils through Toll-like receptor 4. Therefore, our data suggest that Tnc is a relevant mediator of the pathogenic events underlying liver IRI. The data also support the view that studies aimed at further understanding how newly synthesized ECM molecules, such as Tnc, participate in inflammatory responses are needed to improve therapeutic approaches in liver IRI. (Hepatology 2011)
Field-practice study of sorafenib therapy for hepatocellular carcinoma: A prospective multicenter study in Italy
Authors: Iavarone Massimo , Cabibbo Giuseppe , Piscaglia Fabio , Zavaglia Claudio , Grieco Antonio , Villa Erica , Cammà Calogero , Colombo Massimo 
Published: September 2011

Abstract

A multicenter randomized controlled trial established sorafenib as a standard of care for patients with advanced hepatocellular carcinoma (HCC). Because the study was prematurely interrupted due to survival benefits in the sorafenib arm, we conducted an observational study to adequately assess risks and benefits of this regimen in field practice. Starting in 2008, all clinically compensated patients with advanced HCC and those with an intermediate HCC who were unfit or failed to respond to ablative therapies were consecutively evaluated in six liver centers in Italy, for tolerability as well as radiologic and survival response to 800-mg/d sorafenib therapy. Treatment was down-dosed or interrupted according to drug label. Two hundred ninety-six patients (88% Child-Pugh A, 75% Barcelona Clinic Liver Cancer [BCLC]-C, and 25% BCLC-B) received sorafenib for 3.8 months (95% CI 3.3-4.4). Two hundred sixty-nine (91%) patients experienced at least one adverse event (AE), whereas 161 (54%) had to reduce dosing. Treatment was interrupted in 103 (44%) for disease progression, in 95 (40%) for an AE, and in 38 (16%) for liver deterioration. The median survival was 10.5 months in the overall cohort, 8.4 months in BCLC-C versus 20.6 months in BCLC-B patients (

P

< 0.0001), and 21.6 months in the 77 patients treated for >70% of the time with a half dose versus 9.6 months in the 219 patients treated for >70% of the time with a full dose. At month 2 of treatment, the overall radiologic response was 8%. Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic spread of the tumor, radiologic response at month 2, and sorafenib dosing were independent predictors of shortened survival.

Conclusion:

Overall, safety, effectiveness, and generalizability of sorafenib therapy in HCC was validated in field practice. The effectiveness of half-dosed sorafenib may have implications for tailored therapy. (Hepatology 2011)
Alteration of hepatic nuclear receptor-mediated signaling pathways in hepatitis C virus patients with and without a history of alcohol drinking
Authors: Wu Chuanghong , Gilroy Richard , Taylor Ryan , Olyaee Mojtaba , Abdulkarim Bashar , Forster Jameson , O'Neil Maura , Damjanov Ivan , Wan Yu-Jui Yvonne 
Published: September 2011

Abstract

The current study tests a hypothesis that nuclear receptor signaling is altered in chronic hepatitis C patients and that the altered pattern is specific to alcohol drinking history. The expression of a panel of more than 100 genes encoding nuclear receptors, coregulators, and their direct/indirect targets was studied in human livers. Gene expression pattern was compared between 15 normal donor livers and 23 hepatitis C virus (HCV) genotype 1–positive livers from patients without a drinking history (matched for age, sex, and body mass index). HCV infection increased the expression of nuclear receptors small heterodimer partner and constitutive androstane receptor (CAR) as well as genes involved in fatty acid trafficking, bile acid synthesis and uptake, and inflammatory response. However, the expression of retinoid X receptor (RXR) α, peroxisomal proliferator-activated receptor (PPAR) α and β as well as steroid regulatory element-binding protein (SREBP)-1c was decreased in HCV-infected livers. Gene expression pattern was compared in chronic hepatitis C patients with and without a drinking history. Alcohol drinking increased the expression of genes involved in fatty acid uptake, trafficking, and oxidation, but decreased the expression of genes responsible for gluconeogenesis. These changes were consistent with reduced fasting plasma glucose levels and altered expression of upstream regulators that include RXRα, PPARα, and CAR. The messenger RNA levels of fibroblast growth factor 21, interleukin-10, and fatty acid synthase, which are all regulated by nuclear receptors, showed independent correlation with hepatic HCV RNA levels.

Conclusion:

Our findings suggest that those genes and pathways that showed altered expression could potentially be therapeutic targets for HCV infection and/or alcohol drinking-induced liver injury. (Hepatology 2011)
Activation of liver X receptor increases acetaminophen clearance and prevents its toxicity in mice
Authors: Saini Simrat P.S. , Zhang Bin , Niu Yongdong , Jiang Mengxi , Gao Jie , Zhai Yonggong , Lee Jung Hoon , Uppal Hirdesh , Tian Hui , Tortorici Michael A. , Poloyac Samuel M. , Qin Wenxin , Venkataramanan Raman , Xie Wen 
Published: September 2011

Abstract

Overdose of acetaminophen (APAP), the active ingredient of Tylenol, is the leading cause of drug-induced acute liver failure in the United States. As such, it is necessary to develop novel strategies to prevent or manage APAP toxicity. In this report, we reveal a novel function of the liver X receptor (LXR) in preventing APAP-induced hepatotoxicity. Activation of LXR in transgenic (Tg) mice or by an LXR agonist conferred resistance to the hepatotoxicity of APAP, whereas the effect of LXR agonist on APAP toxicity was abolished in LXR-deficient mice. The increased APAP resistance in LXR Tg mice was associated with increased APAP clearance, increased APAP sulfation, and decreased formation of toxic APAP metabolites. The hepatoprotective effect of LXR may have resulted from the induction of antitoxic phase II conjugating enzymes, such as Gst and Sult2a1, as well as the suppression of protoxic phase I P450 enzymes, such as Cyp3a11 and Cyp2e1. Promoter analysis suggested the mouse

Gst

isoforms as novel transcriptional targets of LXR. The suppression of

Cyp3a11

may be accounted for by the inhibitory effect of LXR on the PXR-responsive transactivation of

Cyp3a11

. The protective effect of LXR in preventing APAP toxicity is opposite to the sensitizing effect of pregnane X receptor, constitutive androstane receptor, and retinoid X receptor alpha.

Conclusion:

We conclude that LXR represents a potential therapeutic target for the prevention and treatment of Tylenol toxicity. (Hepatology 2011)
Recombinant adenovirus carrying the hepatocyte nuclear factor-1alpha gene inhibits hepatocellular carcinoma xenograft growth in mice
Authors: Zeng Xin , Lin Yong , Yin Chuan , Zhang Xin , Ning Bei-Fang , Zhang Qing , Zhang Jun-Ping , Qiu Lei , Qin Xiao-Ran , Chen Yue-Xiang , Xie Wei-Fen 
Published: September 2011

Abstract

Hepatocyte nuclear factor-1alpha (HNF1α) is one of the key transcription factors of the HNF family, which plays a critical role in hepatocyte differentiation. Substantial evidence has suggested that down-regulation of HNF1α may contribute to the development of hepatocellular carcinoma (HCC). Herein, human cancer cells and tumor-associated fibroblasts (TAFs) were isolated from human HCC tissues, respectively. A recombinant adenovirus carrying the

HNF1α

gene (AdHNF1α) was constructed to determine its effect on HCC

in vitro

and

in vivo

. Our results demonstrated that HCC cells and HCC tissues revealed reduced expression of HNF1α. Forced reexpression of HNF1α significantly suppressed the proliferation of HCC cells and TAFs and inhibited the clonogenic growth of hepatoma cells

in vitro

. In parallel, HNF1α overexpression reestablished the expression of certain liver-specific genes and microRNA 192 and 194 levels, with a resultant increase in p21 levels and induction of G2/M arrest. Additionally, AdHNF1α inhibited the expression of cluster of differentiation 133 and epithelial cell adhesion molecule and the signal pathways of the mammalian target of rapamycin and transforming growth factor beta/Smads. Furthermore, HNF1α abolished the tumorigenicity of hepatoma cells

in vivo

. Most interestingly, intratumoral injection of AdHNF1α significantly inhibited the growth of subcutaneous HCC xenografts in nude mice. Systemic delivery of AdHNF1α could eradicate the orthotopic liver HCC nodules in nonobese diabetic/severe combined immunodeficiency mice.

Conclusion:

These results suggest that the potent inhibitive effect of HNF1α on HCC is attained by inducing the differentiation of hepatoma cells into mature hepatocytes and G2/M arrest. HNF1α might represent a novel, promising therapeutic agent for human HCC treatment. Our findings also encourage the evaluation of differentiation therapy for tumors of organs other than liver using their corresponding differentiation-determining transcription factor. (Hepatology 2011)