bluuebunny/crossref_metadata_2025_split huggingface dataset:
The road not taken: A path to curing type 1 diabetes?
Authors: Haller Michael J. , Atkinson Mark A. , Schatz Desmond A. 
Published: August 2009

AbstractThe past quarter century has seen a rapid increase in our knowledge about the natural history of autoimmune type 1 diabetes. However, we stand unable to achieve our ultimate goal of preventing or reversing this disease. This viewpoint discusses controversies in current management of type 1 diabetes, the challenges in translating promising studies from mouse models of the disease to humans, hurdles faced in designing optimal prevention and intervention studies, and potential strategies to overcome these obstacles.“....Two roads diverged in a wood, and I‐I took the one less traveled by, And that has made all the difference.” ‐The Road Not Taken Robert Frost, 1920
Animal models of tuberculosis
Authors: Young Douglas 
Published: August 2009

AbstractThere is a wide range of animal models of tuberculosis; which is fortunate, given that there is a wide range of complex biological phenomena to model. Nonetheless, the inadequacy of animal models is a chronic grievance amongst researchers, often expressed in the conclusion that the mouse is not a good model of human tuberculosis. There clearly are major differences between experimental infection of mice and natural infection of humans, but this overarching dogma is inconducive to fruitful research.
EAE: An immunologist's magic eye
Authors: Krishnamoorthy Gurumoorthy , Wekerle Hartmut 
Published: August 2009

AbstractEAE comes in many shapes and colors. Individual variants of EAE present a baffling complexity of different aspects and traits, clinical, immunological, and structural. But, embedded in this seemingly chaotic image, the educated eye will discern patterns that retrace fundamental features of immune response, in particular, autoimmunity and self‐tolerance. EAE and its variants thus can be likened to an autostereogram, i.e. they are an immunologist's magic eye.
Clinical aspects of inflammatory bowel disease
Authors: Siegmund Britta , Zeitz Martin 
Published: August 2009

AbstractInflammatory bowel disease (IBD) accompanies its patients throughout life. Current treatment options do not lead to a cure and are accompanied by significant toxicities. Numerous animal models contributed to the understanding of the pathogenesis of the disease and led to the development of novel treatment strategies. Genome‐wide association analysis added a novel dimension. Here, we discuss how characterization of mutated genes in animal models supports the identification of future therapeutic targets.
Cover Picture: Eur. J. Immunol. 8/09
Authors: Hohlfeld Reinhard 
Published: August 2009

AbstractThe set of scales characterising the differing, but balanced perspectives, of Viewpoint articles forms a distinctive component of the cover image. Combined with the scales is an image taken from the Viewpoint article by Hohlfeld (pp. 2036–2039) that depicts, in cartoon form, the immunopathogenesis of multiple sclerosis. The cartoon portrays activated autoreactive T cells crossing the blood‐brain barrier where, following re‐stimulation, these cells stimulate processes leading to myelin and axon damage. The cartoon is modified from Gijbels K. PhD thesis University of Louvain, 1995 and Hohlfeld, R. Brain 1997. 120: 865–916 and reprinted with permission.
Syntheses and Structures of Tris‐β‐Diketiminate Lanthanide Complexes and Their High Activity for Ring‐Opening Polymerization of ϵ‐Caprolactone and L‐Lactide
Authors: Xue Mingqiang , Jiao Rui , Zhang Yong , Yao Yingming , Shen Qi 
Published: August 2009

AbstractMetathesis of {[(4–XC6H4)NC(Me)]2CH}Li with anhydrous lanthanide trichlorides (LnCl3) in a 3:1 molar ratio yielded a series of tris‐β‐diketiminate complexes with the general formula [LnLX3] [X = Cl, LCl: Ln = Pr (1), Nd (2), Sm (3); X = H, L: Ln = Nd (4); X = Me, LMe: Ln = Nd (5)]. Reaction of sodium salt of β‐diketiminate with anhydrous LnCl3 in a 1:1 molar ratio in thf afforded the corresponding β‐diketiminate lanthanide dichlorides [LClPrCl2(thf)2] (6), [LMeNdCl2(thf)2] (7), and [LNdCl2(thf)2] {L = [(2,6‐iPr2C6H3)NC(Me)]2CH–} (8), respectively. Each of these complexes was characterized, and the molecular structures of complexes 1–5 and 8 were determined by X‐ray single‐crystal structure analysis. Complexes 1–5 were found to be very active single‐component initiators for the ring‐opening polymerization of ϵ‐caprolactone (ϵ‐CL) and L‐lactide (L‐LA) under mild conditions, giving polymers with high molecular weight and moderate polydispersities, whereas complexes 6–8 displayed no activity under the same polymerization conditions. The high catalytic activity shown by tris‐β‐diketiminate lanthanide complexes may be attributed to the activated Ln–β‐diketiminate bond caused by the crowded coordination sphere around the central metal.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Temporary Protection of H‐Phosphinic Acids as a Synthetic Strategy
Authors: Coudray Laëtitia , Montchamp Jean‐Luc 
Published: August 2009

AbstractH‐Phosphinates obtained through various methodologies are protected directly by the reaction with triethyl orthoacetate. The resulting products can be manipulated easily, andvarious synthetic reactions are presented. For example, application to the synthesis of aspartate transcarbamoylase (ATCase) or kynureninase inhibitors are illustrated. Other reactions, such as Sharpless' asymmetric dihydroxylation, or Grubbs' olefin cross‐metathesis are also demonstrated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Numerical study of the turbulent flow in strongly curved stationary and rotating U‐ducts
Authors: Guleren K. Melih 
Published: August 2009

AbstractA large‐eddy simulation (LES) study is undertaken to explore the complex flow of developing turbulent flow through stationary and rotating U‐ducts with strong curvature. Three flow cases are investigated: stationary (non‐rotating), positive and negative rotational cases. Stationary and positive rotational cases are shown to have similar flow characteristics in terms of the mean velocity variations, although the predicted separation zone is nearly doubled in size for positive rotational case. Unlike the positive rotation for which the laminarization effects are observed, turbulence is significantly enhanced for the negative rotation mainly due to the existence of strong secondary flow. Turbulence is found to be highly anisotropic throughout the duct apart from the far downstream regions of the bend for the negative rotational case. The stress–strain relation seems to be completely invalid in the U‐duct apart from the bend region. Copyright © 2009 John Wiley & Sons, Ltd.
Rearrangement of upstream sequences of the hTERT gene during cellular immortalization
Authors: Zhao Yuanjun , Wang Shuwen , Popova Evgenya Y. , Grigoryev Sergei A. , Zhu Jiyue 
Published: August 2009

AbstractTelomerase expression, resulting from transcriptional activation of the hTERT gene, allows cells to acquire indefinite proliferative potential during cellular immortalization and tumorigenesis. However, mechanisms of hTERT gene activation in many immortal cell lines and cancer cells are poorly understood. Here, we report our studies on hTERT activation using genetically related pairs of telomerase‐negative (Tel−) and ‐positive (Tel+) fibroblast lines. First, whereas transiently transfected plasmid reporters did not recapitulate the endogenous hTERT promoter, the promoter in chromosomally integrated bacterial artificial chromosome (BAC) reporters was activated in a subset of Tel+ cells, indicating that activation of the hTERT promoter required native chromatin context and/or distal regulatory elements. Second, the hTERT gene, located near the telomere of chromosome 5p, was translocated in all three Tel+ cell lines but not in their parental precrisis cells and Tel− immortal siblings. The breakage points were mapped to regions upstream of the hTERT promoter, indicating that the hTERT gene was the target of these chromosomal rearrangements. In two Tel+ cell lines, translocation of the endogenous hTERT gene appeared to be the major mechanism of its activation as the activity of hTERT promoter in many chromosomally integrated BAC reporters, with intact upstream and downstream neighboring loci, remained relatively low. Therefore, our results suggest that rearrangement of upstream sequences is an important new mechanism of hTERT promoter activation during cellular immortalization. The chromosomal rearrangements likely occurred during cellular crisis and facilitated by telomere dysfunction. Such translocations allowed the hTERT promoter to escape from the native condensed chromatin environment. © 2009 Wiley‐Liss, Inc.
Extracellular mutant SOD1 induces microglial‐mediated motoneuron injury
Authors: Zhao Weihua , Beers David R. , Henkel Jenny S. , Zhang Wei , Urushitani Makoto , Julien Jean‐Pierre , Appel Stanley H. 
Published: August 2009

AbstractThrough undefined mechanisms, dominant mutations in (Cu/Zn) superoxide dismutase‐1 (mSOD1) cause the non‐cell‐autonomous death of motoneurons in inherited amyotrophic lateral sclerosis (ALS). Microgliosis at sites of motoneuron injury is a neuropathological hallmark of ALS. Extracellular mutant SOD1 (mSOD1) causes motoneuron injury and triggers microgliosis in spinal cord cultures, but it is unclear whether the injury results from extracellular mSOD1 directly interacting with motoneurons or is mediated through mSOD1‐activated microglia. To dissociate these potential mSOD1‐mediated neurotoxic mechanisms, the effects of extracellular human mSOD1G93A or mSOD1G85R were assayed using primary cultures of motoneurons and microglia. The data demonstrate that exogenous mSOD1G93A did not cause detectable direct killing of motoneurons. In contrast, mSOD1G93A or mSOD1G85R did induce the morphological and functional activation of microglia, increasing their release of pro‐inflammatory cytokines and free radicals. Furthermore, only when microglia was co‐cultured with motoneurons did extracellular mSOD1G93A injure motoneurons. The microglial activation mediated by mSOD1G93A was attenuated using toll‐like receptors (TLR) 2, TLR4 and CD14 blocking antibodies, or when microglia lacked CD14 expression. These data suggest that extracellular mSOD1G93A is not directly toxic to motoneurons but requires microglial activation for toxicity, utilizing CD14 and TLR pathways. This link between mSOD1 and innate immunity may offer novel therapeutic targets in ALS. © 2009 Wiley‐Liss, Inc.
Sodium‐dependent vitamin C transporter 2 (SVCT2) is necessary for the uptake of L‐ascorbic acid into Schwann cells
Authors: Gess Burkhard , Lohmann Christina , Halfter Hartmut , Young Peter 
Published: August 2009

AbstractAscorbic acid has been shown to be an essential component for in vitro myelination and to improve the clinical and pathological phenotype of a mouse model of Charcot–Marie‐tooth disease 1A. The mechanism of ascorbic acid uptake into peripheral nerves, however, has not been addressed so far. Hence, we studied the expression and activity of sodium‐dependent vitamin C transporters 1 and 2 (SVCT1 and 2) in the peripheral nervous system. Using immunohistochemistry, immunoblotting, and reverse transcription PCR, we could show that SVCT1 and 2 were differentially expressed in myelinated peripheral nerve fibers and Schwann cell (SC) cultures. SVCT1 was expressed at very low levels confined to the axons, whereas SVCT2 was highly expressed both in the axons and in the SCs. SVCT2 was localized particularly in SC compartments of uncompacted myelin. Uptake assays using 14C‐labeled ascorbic acid showed transport of ascorbic acid into SC cultures. Ascorbic acid transport was dependent on the concentration of sodium, magnesium, and calcium in the extracellular medium. Treatment with the flavonoid phloretin, a known inhibitor of SVCT1 and 2, and specific RNA interference with SVCT2 caused significant reductions in ascorbic acid uptake into SCs. Phloretin‐inhibited uptake of ascorbic acid was further shown in freshly dissected, cell‐culture‐naïve rat sciatic nerves. These results provide evidence for the first time that uptake of ascorbic acid in the peripheral nervous system is crucially dependent on the expression and activity of SVCT2. © 2009 Wiley‐Liss, Inc.
Head and neck cancer radiosensitization by the novel poly(ADP‐ribose) polymerase inhibitor GPI‐15427
Authors: Khan Khurram , Araki Koji , Wang Daiyou , Li Guayan , Li Xin , Zhang Jie , Xu Weizheng , Hoover Randall K. , Lauter Susan , O'Malley Bert , Lapidus Rena G. , Li Daqing 
Published: August 2009

AbstractBackgroundIn this study, we tested the ability of a novel poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, 10‐(4‐methyl‐piperazin‐1‐ylmethyl)‐2H‐7‐oxa‐1,2‐diaza‐benzo[de]‐anthracen‐3‐one (GPI‐15427), to enhance the effect of radiotherapy in a xenograft model of human head and neck squamous cell carcinoma (HNSCC).MethodsHuman xenograft HNSCC tumors were established in female nude mice: animals were treated with orally administered GPI‐15427 at varied doses prior to tumor irradiation. In vitro and in vivo apoptosis analyses and neutral single‐cell gel electrophoresis (comet) assay were performed, with the “tail moment” calculated to evaluate DNA double‐strand break damage.ResultsOrally administered GPI‐15427 given before radiation therapy significantly reduced tumor volume, and cells demonstrated significantly elevated mean tail moments (indicative of DNA damage) and enhanced apoptosis both in vitro and in vivo, compared with radiation‐alone and control groups.ConclusionsUse of the PARP‐1 inhibitor GPI‐15427 induced significant sensitization to radiotherapy, representing a promising new treatment in the management of HNSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Dual priming oligonucleotide–based multiplex PCR analysis for detection of BRAFV600E mutation in FNAB samples of thyroid nodules in BRAFV600E mutation–prevalent area
Authors: Kwak Jin Young , Kim Eun‐Kyung , Kim Jong‐Kee , Han Jeong‐Hyun , Hong Soon Won , Park Tae Sung , Choi Jong Rak 
Published: August 2009

AbstractBackground.To evaluate the diagnostic value of dual priming oligonucleotide (DPO)–based multiplex polymerase chain reaction (PCR) for the detection of BRAFV600E mutations in ultrasound‐guided fine‐needle aspiration biopsy (US‐FNAB) of thyroid nodules.Methods.Our institutional review board approved this retrospective study, and informed consent was not required from patients. The 130 patients underwent US‐FNAB to evaluate BRAF status in thyroid nodules. In FNAB washouts, DPO‐based multiplex PCR, direct DNA sequencing, and PCR–restriction fragment length polymorphism (RFLP) were used to detect BRAFV600E. The diagnostic performance of these methods was calculated. We compared cytologic results by BRAF status.Results.Diagnostic accuracy and sensitivity were highest when screening with DPO‐based multiplex PCR. BRAFV600E positivity was a useful marker at thyroid nodules with “suspicious for papillary thyroid carcinoma” or “inadequate” cytological result.Conclusions.DPO‐based multiplex PCR may be an alternative to direct DNA sequencing because of its high sensitivity, high accuracy, and simplicity. BRAFV600E may be a useful additional diagnostic marker in BRAFV600E‐prevalent areas. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
In vivo and in vitro models of ionizing radiation to the vocal folds
Authors: Saltman Benjamin , Kraus Dennis H. , Szeto Hazel , Parashar Bhupesh , Ghossein Ronald , Felsen Diane , Branski Ryan C. 
Published: August 2009

AbstractBackgroundRadiation therapy (RT) to the head and neck often results in damage to the vocal folds (VF) and surrounding structures. Characterization and treatment of these sequelae is limited, likely due to the lack of experimental models.MethodsLarynges from rats exposed to 2 fractionation schedules (40 Gy total) were analyzed histologically. In vitro, reactive oxygen species (ROS) synthesis, and transcription of select genes associated with ROS, inflammation, and fibrosis were examined in VF fibroblasts after single‐dose radiation.ResultsAlthough radiation‐induced histologic alterations are made to VF architecture, 1 fractionation schedule was accompanied by significant morbidity and mortality. In vitro, radiation increased ROS synthesis and inflammatory and profibrotic gene expression.ConclusionOur data suggest that hyperfractionated RT is more tolerable. Utilizing this model, RT‐induced histologic aberrations are made to the VF mucosa. In addition, a relationship between radiation, ROS, and inflammatory and fibrotic gene expression was observed in vitro. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Land of addicts? an empirical investigation of habit‐based asset pricing models
Authors: Chen Xiaohong , Ludvigson Sydney C. 
Published: August 2009

AbstractThis paper studies the ability of a general class of habit‐based asset pricing models to match the conditional moment restrictions implied by asset pricing theory. We treat the functional form of the habit as unknown, and estimate it along with the rest of the model's finite dimensional parameters. Using quarterly data on consumption growth, assets returns and instruments, our empirical results indicate that the estimated habit function is nonlinear, that habit formation is better described as internal rather than external, and the estimated time‐preference parameter and the power utility parameter are sensible. In addition, the estimated habit function generates a positive stochastic discount factor (SDF) proxy and performs well in explaining cross‐sectional stock return data. We find that an internal habit SDF proxy can explain a cross‐section of size and book‐market sorted portfolio equity returns better than (i) the Fama and French (1993) three‐factor model, (ii) the Lettau and Ludvigson (2001b) scaled consumption CAPM model, (iii) an external habit SDF proxy, (iv) the classic CAPM, and (v) the classic consumption CAPM. Copyright © 2009 John Wiley & Sons, Ltd.
Hox genes of the Japanese eel Anguilla japonica and Hox cluster evolution in teleosts
Authors: Guo Baocheng , Gan Xiaoni , He Shunping 
Published: August 2009

AbstractCompared with other diploid teleosts (2n=48), anguilloid fish have a specialized karyotype (2n=38) and remarkable morphological variation, and represent one basal group species of teleosts. To investigate the Hox gene/cluster inventory in basal teleosts, a PCR‐based survey of Hox genes in the Japanese eel (Anguilla japonica) was conducted with both gene‐specific and homeobox‐targeted degenerate primers. Our data provide evidence that at least 34 distinct Hox genes exist in the Japanese eel genome and that they represent eight Hox clusters. Duplication of Hox genes in the Japanese eel appears to be the result of the fish‐specific genome duplication (FSGD) event. The Japanese eel shared the FSGD event with other teleosts such as zebrafish and pufferfish. A member of Hox paralog group one (HoxA1b) was preserved in the Japanese eel but was lost in other teleosts. Available Hox data revealed that the Hox cluster evolved distinctly in different teleost lineages. All duplicated Hox clusters were retained after the FSGD event in basal teleosts like in the Japanese eel, whereas crown teleosts lost one cluster (HoxCb or HoxDb). Based on current teleostean phylogeny, the HoxDb cluster was lost independently in the teleost lineages Otocephala and Euteleostei. J. Exp. Zool. (Mol. Dev. Evol.) 314B:135–147, 2010. © 2009 Wiley‐Liss, Inc.
Radiosynthesis of [3H]‐ABP688 using [3H]‐methyl nosylate: a non‐volatile alternative methylating agent
Authors: Li Pixu , Olszewski John D. 
Published: August 2009

AbstractTritiated ABP688 was synthesized from desmethyl ABP688 with [3H]‐methyl nosylate in high radiochemical yield. The results demonstrate that [3H]‐methyl nosylate is a good alternative methylating agent for radiosynthesis. Copyright © 2009 John Wiley & Sons, Ltd.
[14C]Dimethyltitanocene and [14C]Methyl(methyltrimethylsilyl) titanocene–Reagents for the [14C]olefination of carbonyl compounds: synthesis of [14C]Aprepitant
Authors: Wallace M. A. , Dean D. C. , Melillo D. G. 
Published: August 2009

AbstractA neurokinin (NK‐1) receptor antagonist, [14C]Aprepitant, was synthesized using two labeled olefination reagents: [14C]dimethyltitanocene 1 and [14C]methyl (methyltrimethylsilyl)titanocene 7. Both reagents can be readily prepared from [14C]methyllithium and have been shown to convert a variety of carbonyls to [14C]methylenes in good radiochemical yields. Copyright © 2009 John Wiley & Sons, Ltd.
Factors affecting the next generation of women leaders: Mapping the challenges, antecedents, and consequences of effective leadership
Authors: McEldowney Rene P. , Bobrowski Paula , Gramberg Anna 
Published: August 2009

AbstractThis article introduces a conceptual model for understanding how young women perceive the current challenges of leadership. Numerous studies and articles claim that women are better educated, more experienced, and better suited for leadership positions than ever before. This news is encouraging, but the number of women in leadership roles in American politics gained less than one percentage point this year, hovering around 22%, while in the private sector many organizations have yet to place a single woman on their board. The proportion of women on corporate boards is 16%, with no evidence that this is likely to grow in the near future. What is even more discouraging is that these low numbers are not significantly higher than those in many developing nations. It is evident that women are underrepresented in top leadership positions and must intensely challenge the status quo. This article presents results of a study based on in‐depth interviews with college women who are seeking paths to leadership. The researchers employ qualitative analytical research tools to explore the complexities of the phenomena. The findings bring a greater understanding of the antecedents and consequences that lie beneath the challenges affecting the next generation of women leaders.
An empirical study of other‐oriented and rational self‐interest leadership approaches
Authors: Barrow Lisa M. S. , Mirabella Jim 
Published: August 2009

AbstractOther orientation is defined as “the extent to which individuals are concerned with the welfare of others” (Meglino & Korsgaard, 2007, p. 59). Other‐oriented leaders focus their attention on organizational objectives coupled with a human resource emphasis, whereas rational self‐interested leaders concern themselves with organizational objectives coupled with self‐emphasis. This quantitative study examines philanthropian and servant leadership, which are other‐oriented leadership approaches, and transactional leadership, which is a rational self‐interested leadership approach, to determine the effectiveness of the approaches in the 21st century. This study further examines the results of a hermeneutic phenomenological study of philanthropian leadership that introduced a new other‐oriented leadership model. This study focuses on leadership preferences of leaders, employees, and third‐year undergraduate business students to determine if there is a significant difference between preferences among groups for other‐oriented and rational self‐interest‐oriented leadership approaches.
Experience matters in principal preparation
Authors: Nelson Sarah W. 
Published: August 2009

AbstractAn act of leadership is always an act of practical theory. We lead because we hold visions of the world as it ought to be, because of the not yet, because of the potential that we see in ideas and people. Yet, there still exists a perceived binary between leadership theory (in the strong sense) and leadership practice, a binary that divides organizations, classrooms, and the differing bodies of leadership literature. In this Symposium, Duncan Waite and his colleagues discuss the barriers they have faced in bringing theory to the educational leadership classroom, as well as the promise they feel theory holds for more productive, equitable, and humane schooling organizations.