bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fundamental issues in systems biology
Authors: O'Malley Maureen A. , Dupré John 
Published: November 2005

AbstractIn the context of scientists' reflections on genomics, we examine some fundamental issues in the emerging postgenomic discipline of systems biology. Systems biology is best understood as consisting of two streams. One, which we shall call ‘pragmatic systems biology’, emphasises large‐scale molecular interactions; the other, which we shall refer to as ‘systems‐theoretic biology’, emphasises system principles. Both are committed to mathematical modelling, and both lack a clear account of what biological systems are. We discuss the underlying issues in identifying systems and how causality operates at different levels of organisation. We suggest that resolving such basic problems is a key task for successful systems biology, and that philosophers could contribute to its realisation. We conclude with an argument for more sociologically informed collaboration between scientists and philosophers. BioEssays 27:1270–1276, 2005. © 2005 Wiley Periodicals, Inc.
Nitric oxide and metastatic cell behaviour
Authors: Williams Emma L. , Djamgoz Mustafa B.A. 
Published: November 2005

AbstractNitric oxide (NO) is a pleiotropic signalling molecule that subserves a wide variety of basic cellular functions and also manifests itself pathophysiologically. As regards cancer and its progression, however, the reported role of NO appears surprisingly inconsistent. In this review, we focus on metastasis, the process of cancer cell spread and secondary tumour formation. In a ‘reductionist’ approach, we consider the metastatic cascade to be made up of a series of basic cellular behaviours (such as proliferation, apoptosis, adhesion, secretion migration, invasion and angiogenesis). We evaluate how NO controls such behaviours, in comparison with normal cells. The available information suggests strongly that NO signalling would be expected to regulate these behaviours both positively and negatively and this probably leads to the observed apparent variability in the NO status of cancer cells and tissues. Thus, the role of NO in cancer is more complex than previously thought. A number of suggestions are made, including consideration of novel mechanisms, such as ion channels, in order to achieve a more consistent and integrated understanding of NO signalling in cancer and to realise its clinical potential. BioEssays 27:1228–1238, 2005. © 2005 Wiley Periodicals, Inc.
Memory mechanisms of active transcription during cell division
Authors: Zhou Guo‐Ling , Liu De‐Pei , Liang Chih‐Chuan 
Published: November 2005

AbstractThe developmental programs of eukaryotic organisms involve the programmed transcription of genes. A characteristic gene expression pattern is established and preserved in each different cell type. Therefore, gene activation at a particular time and its maintenance during cell division are significant for cellular differentiation and individual development. Although many studies have sought to explain the molecular mechanisms of gene expression regulation, the mechanism through which gene expression states are inherited during cell division has not been fully elucidated yet. This review illustrates the general principles and the complexities involved in the establishment and maintenance of active transcription through cell cycles. It focuses on the most‐recent findings about the ways in which molecular memory marks for active transcription are coordinated with cell cycle events, such as replication, mitosis and nuclear organization, to mediate transcription memory across cell division events, which may establish a unifying memory process of active transcription. BioEssays 27:1239–1245, 2005. © 2005 Wiley Periodicals, Inc.
Global analysis of siRNA‐mediated transcriptional gene silencing
Authors: Kavi Harsh H. , Xie Weiwu , Fernandez Harvey R. , Birchler James A. 
Published: November 2005

AbstractThe RNAi machinery is not only involved with post‐transcriptional degradation of messenger RNAs, but also used for targeting of chromatin changes associated with transcriptional silencing. Two recent papers determine the global patterns of gene expression and chromatin modifications produced by the RNAi machinery in fission yeast.(9, 10) The major sites include the outer centromere repeats, the mating‐type locus and subtelomeric regions. By comparison, studies of Arabidopsis heterochromatin also implicate transposons as a major target for silencing. Analyses of siRNA libraries from Drosophila, nematodes and Arabidopsis indicate that major repeats at centromeres, telomeres and transposable elements are likely targets of RNAi. Also, intergenic regions are implicated as targets in Arabidopsis. BioEssays 27:1209–1212, 2005. © 2005 Wiley Periodicals, Inc.
The epigenetic basis for embryonic stem cell pluripotency
Authors: Szutorisz Henrietta , Dillon Niall 
Published: November 2005

AbstractAs well as having the remarkable ability to differentiate into all of the cell types in the embryo, embryonic stem (ES) cells also have the capacity to divide and self‐renew. Maintenance of pluripotency through repeated cell divisions indicates that the developmental plasticity of ES cells has a specific epigenetic basis. We propose that tightly localised regions of histone modification are formed in ES cells by binding of sequence‐specific transcription factors at genes that are destined for expression at later stages of differentiation. These ‘early transcription competence marks’ would help to maintain pluripotency by preventing the spread of repressive chromatin modifications. We further propose that the presence of discrete histone modification marks in pluripotent cells facilitates the binding of lineage‐specific and general transcription factors to the marked regions as ES cells commit to different fates. By helping to organise the precisely timed responses of genes to the signals that determine lineage choice, the gene‐specific localised epigenetic marks would play a key role in the establishment of complex gene expression programmes in differentiating cells. BioEssays 27:1286–1293, 2005. © 2005 Wiley Periodicals, Inc.
Synthesis of Strained Tricyclic β‐Lactams by Intramolecular [2+2] Cycloaddition Reactions of 2‐Azetidinone‐Tethered Enallenols: Control of Regioselectivity by Selective Alkene Substitution
Authors: Alcaide Benito , Almendros Pedro , Aragoncillo Cristina , Redondo María C. , Torres M. Rosario 
Published: November 2005

AbstractA convenient metal‐free methodology for the preparation of structurally novel, strained tricyclic β‐lactams containing a cyclobutane ring has been developed. The first examples accounting for the intramolecular [2+2] cycloaddition reactions in β‐lactams have been achieved by the thermolysis of 2‐azetidinone‐tethered enallenols, which have been prepared in aqueous media by regio‐ and diastereoselective indium‐mediated carbonyl allenylation of 4‐oxoazetidine‐2‐carbaldehydes. Notably, the regioselectivity of the cycloaddition can be tuned in the allene component just by a subtle variation in the substitution pattern of the alkene component.
Synthesis of Donor–Acceptor Alkynylcyclopropanes by Diastereoselective Cyclopropanation of Electron‐Deficient Alkenes with Alkoxyalkynyl Fischer Carbene Complexes
Authors: Barluenga José , Fernández‐Rodríguez Manuel A. , García‐García Patricia , Aguilar Enrique , Merino Isabel 
Published: November 2005

AbstractThe reaction of electron‐deficient alkenes with alkoxyalkynyl Fischer carbene complexes (FCCs) represents a straightforward route to a new type of captodative (donor–acceptor) alkynylcyclopropanes, which have been prepared in moderate to high yields and in a diastereoselective manner. Some studies regarding the employment of additives to facilitate the recovery of the metal moiety after the reaction are also described. Finally, the first example of a cyclopropanation reaction through employing Fischer carbene complexes under microwave irradiation is presented; this method proved to be an advantageous alternative to the thermal reaction.
Water‐Soluble Fluorescent Boronic Acid Compounds for Saccharide Sensing: Substituent Effects on Their Fluorescence Properties
Authors: Zhang Yanling , Gao Xingming , Hardcastle Kenneth , Wang Binghe 
Published: November 2005

AbstractFour new naphthalene‐based boronic acid compounds (1–4) were synthesized. The effect of various carbohydrates on their fluorescence properties has been studied in aqueous phosphate buffer at pH 7.4. Different substitutions on the aniline group of the naphthalene ring resulted in significant differences in fluorescence properties for these four compounds. Compound 1 shows ratiometric fluorescence changes upon addition of a sugar. Compounds 2 and 3 do not show ratiometric fluorescence changes but show very large fluorescence intensity changes (about 70‐fold fluorescence intensity increase). In addition to the quantifiable fluorescence property changes upon sugar addition, the fluorescence color changes of 1–3 are also visible to the naked eye. However, amidation of the aniline nitrogen atom significantly diminishes the fluorescence intensity of compound 4. The crystal structure of one boronic acid provided some insight into the structural features that are important for the fluorescence properties of these compounds.
Phase II study of weekly irinotecan plus capecitabine for chemotherapy‐naive patients with advanced nonsmall cell lung carcinoma
Authors: Han Ji‐Youn , Lee Dae Ho , Lee Sung Young , Park Chun Gun , Kim Hyae Young , Lee Hong Gi , Lee Jae Jin , Kim Heung Tae , Lee Jin Soo 
Published: November 2005

AbstractBACKGROUNDA Phase II study was conducted to evaluate the efficacy and toxicity of an irinotecan plus capecitabine combination, a new nonplatinum regimen, in chemonaive patients with advanced nonsmall cell lung carcinoma (NSCLC).METHODSBetween July 2003 and April 2004, 53 patients with a histologically confirmed diagnosis of NSCLC were enrolled. All but 5 patients were male, 52 (98%) had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, 39 (74%) had AJCC Stage IV disease, and the median age was 61 years. Treatment consisted of intravenous irinotecan at a dose of 90 mg/m2 on Days 1 and 8 and oral capecitabine at a dose of 1000 mg/m2 twice daily on Days 1–14 of each 21‐day cycle, given up to 12 cycles.RESULTSOf 53 patients enrolled, 22 achieved objective tumor responses (all partial responses) for an overall response rate of 41.5% (95% confidence interval [95% CI], 28.2–54.8%). After a median follow‐up of 17.4 months, the median survival was 14.6 months with a 1‐year survival rate of 60.1% (95% CI, 46.9–73.4%) and a median progression‐free survival of 5.1 months. Treatment was very well tolerated, with only 10% of patients experiencing NCI‐CTC Grade 3 or 4 toxicities. The most common toxicities were hand–foot syndrome and diarrhea. In multiple logistic regression analysis for overall response, only the stage predicted for significantly better response (P = 0.04). Squamous cell carcinoma was marginally predictive for better response (P = 0.08).CONCLUSIONSThe irinotecan plus capecitabine regimen demonstrated an antitumor activity that is favorably comparable with other commonly used cisplatin‐based regimens. Given the mild toxicity profile and favorable survival outcome, this nonplatinum regimen warrants further evaluation in a randomized trial. Cancer 2005. © 2005 American Cancer Society.
Clinical trial of valproic acid and all‐trans retinoic acid in patients with poor‐risk acute myeloid leukemia
Authors: Bug Gesine , Ritter Markus , Wassmann Barbara , Schoch Claudia , Heinzel Thorsten , Schwarz Kerstin , Romanski Annette , Kramer Oliver H. , Kampfmann Manuela , Hoelzer Dieter , Neubauer Andreas , Ruthardt Martin , Ottmann Oliver G. 
Published: November 2005

AbstractBACKGROUNDValproic acid (VPA), a histone deacetylase (HDAC) inhibitor, induced in vitro differentiation of primary acute myeloid leukemia (AML) blasts, an effect enhanced by all‐trans retinoic acid (ATRA). Clinical responses to VPA were recently observed in patients with myelodysplastic syndrome (MDS). Herein, the authors have described results of a clinical trial with VPA plus ATRA in 26 patients with poor‐risk AML.METHODSVPA (5–10 mg/kg starting dose) and ATRA (45 mg/m2) were administered orally. Low‐dose AraC or hydroxyurea were permitted to control leukocytosis. Biologic activity of VPA was confirmed by serial analysis of HDAC2 protein levels in peripheral blood (PB) mononuclear cells.RESULTSNineteen of 26 patients completed at least 4 weeks of VPA/ATRA treatment; 7 patients were withdrawn prematurely because of rapidly progressive disease (n = 3) or unacceptable neurologic and cardiovascular toxicity (n = 4). Additional cytoreductive treatment was required in 58% of patients enrolled. Median treatment duration was 3 months. No patient achieved complete remission, one with de novo AML had a minor response, and two patients with secondary AML arising from myeloproliferative disorder (MPD) achieved a partial remission and clearance of PB blasts, respectively. The latter responses were accompanied by profound granulocytosis and erythrocytosis in both patients, reminiscent of the response pattern known from ATRA treatment of acute promyelocytic leukemia. However, cytogenetic analysis of isolated CD34+ cells and granulocytes did not reveal terminal differentiation of leukemic blasts.CONCLUSIONSTreatment with VPA/ATRA results in transient disease control in a subset of patients with AML that has evolved from a myeloproliferative disorder but not in patients with a primary or MDS‐related AML. Cancer 2005. © 2005 American Cancer Society.
Capecitabine combined with gemcitabine (CapGem) as first‐line treatment in patients with advanced/metastatic biliary tract carcinoma
Authors: Cho Jae Yong , Paik Yong Han , Chang Yoon Soo , Lee Se Joon , Lee Dong‐Ki , Song Si Young , Chung Jae Bock , Park Mi‐Suk , Yu Jeong‐Sik , Yoon Dong‐Sup 
Published: November 2005

AbstractBACKGROUNDBiliary tract carcinoma is an aggressive cancer, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A Phase II trial was conducted to study a combination of oral capecitabine and gemcitabine (CapGem) as first‐line therapy in patients with advanced and/or metastatic biliary carcinoma.METHODSPatients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients had histologically or cytologically confirmed, measurable adenocarcinoma and had not received prior therapy with capecitabine or gemcitabine. Treatment consisted of intravenous (i.v.) gemcitabine (1000 mg/m2 on Days 1 and 8) plus oral capecitabine (650 mg/m2 twice daily on Days 1–14) every 3 weeks for up to 6 cycles. Tumor response, survival, and safety were determined.RESULTSA total of 44 patients were evaluable. Primary tumor sites were: intrahepatic (n = 14) and extrahepatic biliary duct (n = 16); gallbladder (n = 7); and ampulla (n = 7). Fourteen (32%) patients had a partial response and 15 (34%) patients had stable disease. Median time to disease progression and overall survival were 6.0 (range, 3.8–8.1) and 14 (range, 11.4–16.6) months, respectively. The 1‐year survival rate was 58%. No Grade 4 adverse events were seen. Transient Grade 3 neutropenia/thrombocytopenia and manageable (almost invariably Grade 2) nausea, diarrhea, and hand–foot syndrome were the most common adverse events.CONCLUSIONSCapGem is an active and well tolerated first‐line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma that offers a convenient home‐based therapy. Cancer 2005. © 2005 American Cancer Society.
Influence of Coadsorbates on the NO Dissociation on a Rhodium(311) Surface
Authors: Inderwildi Oliver R. , Lebiedz Dirk , Deutschmann Olaf , Warnatz Jürgen 
Published: November 2005

AbstractDensity functional theory (DFT) studies were performed to investigate the influence of coadsorbates on the nitrogen oxide dissociation on the vicinal rhodium(311) surface. This study amplifies prior studies on the dissociation of oxygen and nitrogen oxide on the (111) facet of rhodium. The influence of coadsorbates on the kinetic parameters and thermochemistry of the NO dissociation on Rh(311) was studied. In addition, the activation energy and thermochemistry of this reaction were determined as a function of oxygen preoccupation/initial coverage. Steric and electronic effects and their influence on the dissociation reaction were examined. The results are discussed in the face of an NOx dissociation catalyst system proposed by Nakatsuji.
Confirmatory factor analysis of a short form of the Coping Inventory for Stressful Situations
Authors: Cohan Sharon L. , Jang Kerry L. , Stein Murray B. 
Published: November 2005

AbstractThe 48‐item Coping Inventory for Stressful Situations (CISS) was designed to assess three dimensions (task‐oriented, emotional, and avoidant) of self‐reported responses to stressful circumstances, but results from factor analyses suggest four factors. The present research used confirmatory factor analysis to verify the four‐factor structure for the 21‐item CISS short form in samples of 1,628 undergraduate students and 390 community‐dwelling adults. Factors corresponding to task‐oriented and emotional scales were orthogonal and were well defined by their seven constituent items. The avoidant scale was split into two three‐item parcels that describe specific avoidance behaviors (contact a friend and treat oneself) rather than broad response categories. In the undergraduate sample, depression and anxiety correlated negatively with the task‐oriented scale and positively with the emotional scale. In the community sample, the emotional scale was positively correlated with neuroticism and negatively correlated with extroversion and agreeableness, whereas the task‐oriented scale was negatively correlated with neuroticism and positively correlated with extroversion, openness, agreeableness, and conscientiousness. It was concluded that the task‐oriented and emotional scales have potential as measures of two types of responses to routine stressors. © 2005 Wiley Periodicals, Inc. J Clin Psychol 62: 273–283, 2006.
Phenotypic accommodation: adaptive innovation due to developmental plasticity
Authors: West‐Eberhard Mary Jane 
Published: November 2005

AbstractPhenotypic accommodation is adaptive adjustment, without genetic change, of variable aspects of the phenotype following a novel input during development. Phenotypic accommodation can facilitate the evolution of novel morphology by alleviating the negative effects of change, and by giving a head start to adaptive evolution in a new direction. Whether induced by a mutation or a novel environmental factor, innovative morphological form comes from ancestral developmental responses, not from the novel inducing factor itself. Phenotypic accommodation is the result of adaptive developmental responses, so the novel morphologies that result are not “random” variants, but to some degree reflect past functionality. Phenotypic accommodation is the first step in a process of Darwinian adaptive evolution, or evolution by natural selection, where fitness differences among genetically variable developmental variants cause phenotype‐frequency change due to gene‐frequency change.J. Exp. Zool. (Mol. Dev. Evol.) 304B, 2005. © 2005 Wiley‐Liss, Inc.
Quantitative measurement of hepatitis B virus DNA in different areas of hepatic lobules in patients with chronic hepatitis B
Authors: Mishiro Tomoko , Hamamoto Sachiko , Furuta Koichiro , Ishimura Norihisa , Rumi M.A.K. , Miyake Tatsuya , Sato Shuichi , Ishihara Shunji , Adachi Kyoichi , Kinoshita Yoshikazu 
Published: November 2005

AbstractLiver histology in chronic hepatitis B is marked by inflammatory infiltration involving the peripheral zones. The cause of such cellular infiltration remains unknown. The aim of the present study was to investigate the amounts of intrahepatic hepatitis B virus (HBV) DNA separately in the peripheral and central zones, using laser capture microdissection coupled with real‐time quantitative polymerase chain reaction. Fourteen patients with chronic hepatitis B were included in the study. Liver biopsy samples were taken and hepatocytes were microdissected separately from peripheral and central zones. DNA was extracted from hepatocytes in each zone and evaluated the amounts of HBV‐DNA. Immunohistochemical study for hepatitis B core antigen (HBcAg) was also performed. The amounts of total intrahepatic HBV‐DNA in patients positive for hepatitis Be antigen (HBeAg) were greater than those in HBeAg‐negative patients. There was no difference in HBV‐DNA between the peripheral and central zones. Immunohistochemistry also showed that HBcAg‐positive cells were distributed homogeneously in the hepatic lobules. In patients with peripherally predominant HBV‐DNA, the serum alanine aminotransferase (ALT) level was lower than in patients with centrally predominant HBV‐DNA. HBV‐DNA was distributed homogeneously in the hepatic lobules. In patients with lower amounts of HBV‐DNA in the peripheral zone, the serum ALT level tended to be higher than in other patients. J. Med. Virol. 78:37–43, 2006. © 2005 Wiley‐Liss, inc.
Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers
Authors: Datta Sibnarayan , Banerjee Arup , Chandra Partha K. , Chowdhury Abhijit , Chakravarty Runu 
Published: November 2005

AbstractOccult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in the serum in absence of hepatitis B surface antigen (HBsAg). Studies were conducted to screen for occult HBV infection among family members of HBV carriers, incidentally detected positive for HBV infection with a view to assess the pattern of virus transmission among them. Nested PCR assay, employing independent sets of primers to surface and core genes, was used for detection of HBV DNA in serum samples from 28 index cases with asymptomatic HBV infection, and in serum samples from 72 HBsAg negative/anti‐HBc positive family members. HBV DNA was detected in 15 HBsAg negative family members of 10 HBsAg positive index patients and was studied in detail. Direct sequencing of S gene region of 25 isolates (10 index cases and 15 contacts) and phylogenetic analysis with data base sequences revealed that genotypes A, C, and D and subtype adw2, adr, and ayw3 were present among them. Evidence of transmission from outside family sources was found in addition to intrafamilial transmission among individuals with occult infection. Mutations in the major hydrophilic loop (MHL) of the S gene region were also detected, including the ‘vaccine escape’ mutation G145R in three cases. Although majority of the occult infection was associated with low viral load, 3/15 (20%) cases were with higher viral load and potential infectivity. These cases are especially notable in diagnostic, blood banking, and transplantation services. J. Med. Virol. 78:53–59, 2006. © 2005 Wiley‐Liss, inc.