bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional segregation of cortical language areas by sentence repetition
Authors: Dehaene‐Lambertz Ghislaine , Dehaene Stanislas , Anton Jean‐Luc , Campagne Aurelie , Ciuciu Philippe , Dehaene Guillaume P. , Denghien Isabelle , Jobert Antoinette , LeBihan Denis , Sigman Mariano , Pallier Christophe , Poline Jean‐Baptiste 
Published: March 2006

AbstractThe functional organization of the perisylvian language network was examined using a functional MRI (fMRI) adaptation paradigm with spoken sentences. In Experiment 1, a given sentence was presented every 14.4 s and repeated two, three, or four times in a row. The study of the temporal properties of the BOLD response revealed a temporal gradient along the dorsal–ventral and rostral–caudal directions: From Heschl's gyrus, where the fastest responses were recorded, responses became increasingly slower toward the posterior part of the superior temporal gyrus and toward the temporal poles and the left inferior frontal gyrus, where the slowest responses were observed. Repetition induced a decrease in amplitude and a speeding up of the BOLD response in the superior temporal sulcus (STS), while the most superior temporal regions were not affected. In Experiment 2, small blocks of six sentences were presented in which either the speaker voice or the linguistic content of the sentence, or both, were repeated. Data analyses revealed a clear asymmetry: While two clusters in the left superior temporal sulcus showed identical repetition suppression whether the sentences were produced by the same speaker or different speakers, the homologous right regions were sensitive to sentence repetition only when the speaker voice remained constant. Thus, hemispheric left regions encode linguistic content while homologous right regions encode more details about extralinguistic features like speaker voice. The results demonstrate the feasibility of using sentence‐level adaptation to probe the functional organization of cortical language areas. Hum Brain Mapp, 2006. © 2006 Wiley‐Liss, Inc.
Synthesis of 2‐Azabicyclo[3.2.2]nonane‐Derived Monosaccharide Mimics and Their Evaluation as Glycosidase Inhibitors
Authors: Buser Stephan , Vasella Andrea 
Published: March 2006

AbstractThe racemic 2‐azabicyclo[3.2.2]nonanes 5 and 18 were synthesized and tested as β‐glycosidase inhibitors. The intramolecular Diels–Alder reaction of the masked o‐benzoquinone generated from 2‐(allyloxy)phenol (6) gave the α‐keto acetal 7 which was reduced with SmI2 to the hydroxy ketone 8. Dihydroxylation, isopropylidenation (→ 12), and Beckmann rearrangement provided lactam 15. N‐Benzylation of this lactam, reduction to the amine 17, and deprotection provided the amino triol 19 which was debenzylated to the secondary amine 5. Both 5 and 19 proved weak inhibitors of snail β‐mannosidase (IC50 > 10 mM), Caldocellum saccharolyticum β‐glucosidase (IC50 > 10 mM), sweet almond β‐glucosidase (IC50 > 10 mM), yeast α‐glucosidase (5: IC50 > 10 mM; 19: IC50 = 1.2 mM), and Jack bean α‐mannosidase (no inhibition detected).
The First Ring‐Enlargement of a 1‐Azabicyclo[1.1.0]butane to a 1‐Azabicyclo[2.1.1]hexane
Authors: Mlostoń Grzegorz , Heimgartner Heinz 
Published: March 2006

AbstractThe reactions of 3‐phenyl‐1‐azabicyclo[1.1.0]butane (4) with dimethyl dicyanofumarate ((E)‐8) and dimethyl dicyanomaleate ((Z)‐8) lead to the same mixture of cis‐ and trans‐4‐phenyl‐1‐azabicyclo[2.1.1]hexane 2,3‐dicarboxylates (cis‐11 and trans‐11, resp.; Scheme 3). This result of a formal cycloaddition to the central CN bond of 4 is interpreted by a stepwise reaction mechanism via a relatively stable zwitterionic intermediate 10, which could be intercepted by morpholine to give a 1 : 1 : 1 adduct 12, which undergoes a spontaneous elimination of HCN to yield the fumarate 13 (Scheme 4).
Two New Compounds from the Ascomycete Daldinia concentrica
Authors: Qin Xiang‐Dong , Dong Ze‐Jun , Liu Ji‐Kai 
Published: March 2006

AbstractTwo new compounds, 1‐isopropyl‐2,7‐dimethylnaphthalene (1) and 21‐(acetyloxy)‐6,13,14‐trihydroxy‐16,18‐dimethyl‐10‐phenyl[11]cytochalasa‐7,19‐dien‐1‐one (2), were isolated from the fruiting bodies of Daldinia concentrica. The structures were established by spectroscopic methods.
Numerical Simulation of the Pressure Denaturation of a Helical β‐Peptide Heptamer Solvated in Methanol
Authors: Gee Peter J. , van Gunsteren Wilfred F. 
Published: March 2006

AbstractThe effect of elevated pressure on the conformational behavior of a β‐peptide heptamer (1) in MeOH solution was considered. The response of the peptide to elevated pressure was probed by means of molecular dynamics (MD) simulations, and described in atomic terms. The most‐striking features of the response are that the region of the ‘unfolded’ state of the peptide accessible at elevated pressure is narrow, and that thermal and pressure denaturation produce similar ‘unfolded’ states in the case of 1.
Solid‐Supported Green Synthesis of Substituted Hydrocinnamic Esters by Focused Microwave Irradiation
Authors: Kumar Vinod , Sharma Anuj , Sinha Arun K. 
Published: March 2006

AbstractAn efficient chemoselective hydrogenation protocol for substituted cinnamic esters is developed for the synthesis in quantitative yield of corresponding bioactive dihydrocinnamic esters with solid‐supported palladium chloride/ammonium formate (cat.) in HCOOH/H2O 1 : 2 as a hydrogenating agent under focused‐microwave irradiation for 10 min.
Reaction of Elemol with Acetic Acid/Perchloric Acid: Characterization of a Novel Oxide and (+)‐β‐Cyperone
Authors: Wahidulla Solimabi , Govenkar Mangala Babu , Paknikar Sashikumar Keshav 
Published: March 2006

AbstractThe minor unidentified compounds of the acetic acid/perchloric acid dehydration of elemol (1) were fully characterized. The structure and relative configuration of the less polar fragrant compound 2, named elemoxide, was deduced by 1D‐ and 2D‐NMR data including C,C‐connectivity, NOE, and NOESY experiments. The absolute configuration was established as (3S,3aR,7aR)‐1,3,3a,4,7,7a‐hexahydro‐6‐isopropyl‐1,1,3,3a‐tetramethylisobenzofuran (2) on the basis of its preparation from elemol (1). (+)‐β‐cyperone (3), a known sesquiterpene, was also identified as a minor product of the reaction. A plausible mechanistic explanation for the formation of elemoxide (2) and (+)‐β‐cyperone (3) is presented.
Paranolin: a New Xanthene‐Based Metabolite from Paraphaeosphaeria nolinae
Authors: Ge Hui Ming , Song Yong Chun , Chen Jing Rong , Hu Sha , Wu Jian Yong , Tan Ren Xiang 
Published: March 2006

AbstractA new xanthene‐based, polycyclic metabolite, paranolin (= (2R,3aS,12aR)‐3,3a‐dihydro‐3a‐hydroxy‐8‐(hydroxymethyl)‐2‐(1‐hydroxy‐1‐methylethyl)‐9‐methoxy‐10‐methylfuro[3,2‐d]xanthen‐6(2H)‐one; 1) was isolated from a culture of Paraphaeosphaeria nolinae (IFB‐E011), an endophytic fungus residing in the normal stem of the artemisinin‐producing plant Artemisia annua (Asteraceae). The structure of 1 was elucidated by extensive spectroscopic analyses. Although not substantially active against the human colon (SW1116) and human cervical carcinoma (Hela) cell lines, this metabolite seems to be the first example of a xanthene‐derived secondary metabolite. Its possible biosynthetic origin (Scheme) and its significance as a phyllogenetic marker are discussed in brief.
A Practical, Water‐Soluble, Ionic Scavenger for the Solution‐Phase Syntheses of Amides
Authors: Lei Ming , Tao Xiao‐Le , Wang Yan‐Guang 
Published: March 2006

AbstractA new ionic, water‐soluble scavenger for acyl chlorides, 1‐(2‐aminoethyl)pyridinium bromide (1), has been investigated. Compound 1 was used for the rapid and simple purification of a series of benzamides and sulfonamides (Table) obtained by solution‐phase synthesis from the corresponding amines (Scheme). The inexpensive scavenger, which can be prepared on large scale, was shown to readily ‘eliminate’ excess acyl chlorides (reagent) by simple aqueous extraction. The amides purified in this way were obtained in excellent yields and purities (Table), which makes 1 a versatile new reagent, especially for the combinatorial solution‐phase synthesis of amide libraries.
Three New, 1‐Oxygenated ent‐8,9‐Secokaurane Diterpenes from Croton kongensis
Authors: Chen Wei , Yang Xiao‐Dong , Zhao Jing‐Feng , Yang Jing‐Hua , Zhang Hong‐Bin , Li Zi‐Yan , Li Liang 
Published: March 2006

AbstractThree new ent‐8,9‐secokaurane diterpenes, kongensins A–C (1–3), were isolated from the aerial parts of Croton kongensis, together with two known compounds, rabdoumbrosanin (4) and (7α,14β)‐7,14‐dihydroxy‐ent‐kaur‐16‐en‐15‐one (5). The structures of the new compounds were elucidated by HR‐MS as well as in‐depth 1D‐ and 2D‐NMR analyses. Compounds 1–3 showed an unusual oxygenation pattern, with an AcO or OH group at C(1), in combination with a Δ8(14) unsaturation (1) or an 8,14‐epoxide function (2, 3).
Enantioselective Synthesis of (−)‐(19R)‐Ibogamin‐19‐ol
Authors: Höck Stefan , Borschberg Hans‐Jürg 
Published: March 2006

AbstractThe first total synthesis of the natural product (−)‐(19R)‐ibogamin‐19‐ol ((−)‐1) is reported (biogenetic atom numbering). Starting with L‐glutamic acid from the chiral pool and (2S)‐but‐3‐en‐2‐ol, the crucial aliphatic isoquinuclidine (= 2‐azabicyclo[2.2.2]octane) core containing the entire configurational information of the final target was prepared in 15 steps (overall yield: 15%). The two key steps involved a highly effective, self‐immolating chirality transfer in an Ireland–Claisen rearrangement and an intramolecular nitrone‐olefin 1,3‐dipolar cycloaddition reaction (Scheme 3). Onto this aliphatic core was grafted the aromatic moiety in the form of N(1)‐protected 1H‐indole‐3‐acetic acid by application of the dicyclohexylcarbodiimide (DCC) method (Scheme 4). Four additional steps were required to adjust the substitution pattern at C(16) and to deprotect the indole subunit for the closure of the crucial 7‐membered ring present in the targeted alkaloid family (Schemes 4 and 5). The spectral and chiroptical properties of the final product (−)‐1 matched the ones reported for the naturally occurring alkaloid, which had been isolated from Tabernaemonatana quadrangularis in 1980. The overall yield of the entire synthesis involving a linear string of 20 steps amounted to 1.9% (average yield per step: 82%).
A New Cembranoid Diterpene and Other Related Metabolites from the South‐China‐Sea Soft Coral Lobophytum crassum
Authors: Yin Shuai‐Wen , Shi Yan‐Ping , Li Xiao‐Ming , Wang Bin‐Gui 
Published: March 2006

AbstractA new hydroperoxy‐substituted cembranoid diterpene, 2‐hydroperoxysarcophine (= (1aR*,4E,11E,14aR*)‐2,3,6,7,10a,13,14,14a‐octahydro‐10a‐hydroperoxy‐1a,5,8,12‐tetramethyloxireno[9,10]cyclotetradeca[1,2‐b]furan‐9(1aH)‐one; 1), was isolated from the marine soft coral Lobophytum crassum. Also isolated were two other cembranoid diterpenes, obtained for the first time from a natural source, i.e., 7β,8β‐epoxy‐4α‐hydroxycembra‐1(15),2,11‐trien‐16,2‐olide (2) and 7β,8β‐epoxy‐4β‐hydroxycembra‐1(15),2,11‐trien‐16,2‐olide (3), along with three further cembranoid derivatives, five sterols, and two open‐chain metabolites. Their structures and relative configurations were elucidated on the basis of extensive spectroscopic analyses including 1D‐ and 2D‐NMR, and HR‐ESI‐MS experiments.
Molecular determinants of response to RTK‐targeting agents in nonsmall cell lung cancer
Authors: Reinmuth Niels , Meister Michael , Muley Thomas , Steins Martin , Kreuter Michael , Herth Felix J.F. , Hoffmann Hans , Dienemann Hendrik , Thomas Michael 
Published: March 2006

AbstractReceptor tyrosine kinases (RTKs) are essential components of the cellular signaling apparatus and are often mutated or otherwise deregulated in nonsmall cell lung cancer (NSCLC). These receptors are not solely expressed by cancer cells but also by multiple other cell types, including stromal cells that, in turn, may modulate cancer cell functions by various direct and indirect interactions. Recently, clinical studies have successfully evaluated the inhibition of RTKs by specific RTK‐targeting agents, including tyrosine kinase inhibitors (TKIs). Although the response was impressive in some studies, only a limited proportion of patients benefit from these new drugs. Therefore, an intensive search for markers has started to determine which patients and tumor types are most likely to respond favorably to this new kind of treatment. Considerable attention has been focused onto molecular changes in cancer cells such as receptor expression, gene amplification, changes in intracellular signaling and receptor mutations. In this article, we explore the current data regarding molecular alterations as surrogate markers of response to specific RTK‐targeting agents in NSCLC. Defined alterations may serve as key markers helping to preselect NSCLC patients for an individualized therapeutic approach in the future. © 2006 Wiley‐Liss, Inc.
Bystander effects are induced by CENU treatment and associated with altered protein secretory activity of treated tumor cells A relay for chemotherapy?
Authors: Demidem Aicha , Morvan Daniel , Madelmont Jean Claude 
Published: March 2006

AbstractIn a previous study, it was reported that secondary untreated melanoma tumors implanted several weeks after and at distance from primary chloroethylnitrosourea (CENU)‐treated tumors underwent differentiation and growth inhibition. To see whether the primary treated tumor released soluble factors that mediated the secondary tumor response, serum transfer experiments were performed in vivo. Administration of serum from CENU‐treated tumor‐bearing donors arrested tumor proliferation, decreased vessel formation and induced tumor metabolite alterations encompassing glutathione decrease and polyunsaturated fatty acid and phosphoethanolamine increase. These changes mimicked secondary tumor phenotype. To reproduce the model in vitro, cell culture supernatant transfer experiments were performed. CENU‐treated cell cultures showed polyploidy and reactive oxygen species (ROS) production. Cell cultures challenged by a conditioned medium of CENU‐treated cells underwent growth inhibition, cytoskeleton disorders, cytokinesis retardation, metabolite alterations, glutathione decrease and phosphoethanolamine increase, without ROS elicitation. Proteomics of CENU‐treated cell conditioned media revealed altered protein secretion activity by CENU‐treated cells. Among de novo secreted proteins, the most expressed were phosphatidylethanolamine‐binding protein (PEBP), cardiovascular heat shock protein (cHsp), Rho‐associated coiled‐coil forming kinase 2 (ROCK) and actin fragments. These proteins testified of cytoskeleton disorders, growth inhibition and metabolite alterations. This article demonstrates the release by CENU‐treated tumors of growth inhibitory differentiation‐inducing soluble factors. These factors mediate remote bystander effects and attest persistent biological activity of residual tumors after chemotherapy. © 2006 Wiley‐Liss, Inc.
Tumor iNOS predicts poor survival for stage III melanoma patients
Authors: Ekmekcioglu Suhendan , Ellerhorst Julie A. , Prieto Victor G. , Johnson Marcella M. , Broemeling Lyle D. , Grimm Elizabeth A. 
Published: March 2006

AbstractInducible nitric oxide synthase (iNOS) produces nitric oxide, which has growth promoting activity in melanoma. A preliminary study of tumors from patients with Stage III melanoma who had received neo‐adjuvant therapy revealed an association of tumor iNOS expression with shortened survival. The objective of the present study was to determine whether iNOS expression in tumors of newly diagnosed, untreated Stage III patients is predictive of survival. iNOS expression was examined by immunohistochemistry in tumors from 132 patients. The staining was evaluated for percentage of positive cells (Number score) and the intensity of staining (Intensity score). The association of iNOS expression with overall and disease‐specific survival was tested in univariate and multivariate Cox proportional hazards regression models that included other known prognostic factors. Results of the univariate analysis demonstrated that the presence of iNOS in a patient's tumor, whether graded on the basis of Number or Intensity score, was associated with a significant increase in the hazard ratio of death from melanoma. These findings were corroborated by median survival data estimated from Kaplan Meier analysis. In the multivariate model including iNOS number or intensity, gender, age, number of lymph nodes, macroscopic disease and in‐transit disease, only iNOS expression predicted survival. We conclude that a significant association exists between tumor iNOS expression and shortened survival in untreated Stage III melanoma patients. The ability of iNOS to predict outcomes for these patients may be independent of other known prognostic factors, providing a new molecular marker with significant potential for clinical utility. © 2006 Wiley‐Liss, Inc.
Proteasome inhibition with bortezomib: A new therapeutic strategy for non‐Hodgkin's lymphoma
Authors: Leonard John P. , Furman Richard R. , Coleman Morton 
Published: March 2006

AbstractThe incidence of non‐Hodgkin's lymphoma (NHL) has markedly increased in the US and other westernized countries in recent years and presents a considerable clinical challenge. NHL is divided into subtypes that follow an aggressive or indolent course. Follicular lymphoma (FL), the most common indolent subtype, and mantle cell lymphoma (MCL), an aggressive subtype that accounts for approximately 5% of cases, are generally incurable. MCL has a relatively poor prognosis, with a median survival of 3–4 years. Despite improving response rates with new agents and regimens, the lack of demonstrated improvement in overall survival in many subtypes supports the development of novel approaches, such as proteasome inhibition. Bortezomib is the first proteasome inhibitor to be evaluated in human studies. It has already been approved as second‐line treatment in multiple myeloma and is now under active investigation in NHL. The US FDA has granted bortezomib fast‐track designation for relapsed and refractory MCL. In vitro and in vivo studies have demonstrated single‐agent activity against various lymphoid tumors, and additive or synergistic effects in combination with other agents, including standard chemotherapy drugs employed in NHL. Phase 2 clinical trials indicate that bortezomib is well tolerated and active in several NHL subtypes, with response rates of 18–60% in FL and 39–56% in MCL. A number of combination trials are currently underway with a range of standard agents. Bortezomib has the potential to play a significant role throughout the NHL treatment algorithm in the future. © 2006 Wiley‐Liss, Inc.
Synergistic effects of docetaxel and S‐1 by modulating the expression of metabolic enzymes of 5‐fluorouracil in human gastric cancer cell lines
Authors: Wada Yoshiyuki , Yoshida Kazuhiro , Suzuki Takahisa , Mizuiri Hirozumi , Konishi Kazuo , Ukon Kei , Tanabe Kazuaki , Sakata Yu , Fukushima Masakazu 
Published: March 2006

AbstractWe have recently demonstrated in a Phase I/II study that combination chemotherapy with docetaxel (TXT) and S‐1 is active against metastatic gastric carcinomas. To elucidate the mechanisms underlying the synergistic effects of these drugs, both the growth inhibitory effects and the expression profiles of enzymes involved in fluorouracil (5‐FU) metabolism were examined in vitro and in vivo. TXT alone and in combination with 5‐FU inhibited the growth of each of the 5 gastric cancer cell lines that we examined (TMK‐1, and MKN‐1, ‐28, ‐45 and ‐74), in a time‐ and dose‐dependent manner. Moreover, striking synergistic effects were observed in TMK‐1 cells in vitro with IC50 values of between 4.73 and 0.61 nM 5‐FU. Furthermore, in TMK‐1 xenografts, 5‐FU/TXT cotreatments exhibited synergistic antitumor effects. The combination of S‐1 and TXT, however, exhibited greater growth‐inhibitory effects than the 5‐FU/TXT cotreatments. The mechanisms underlying these synergistic effects of S‐1 and TXT were examined by expression and activity analyses of the 5‐FU metabolic enzymes. The expression of thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) were decreased 50 and 73% of control levels, respectively, and that of orotate phosphorybosyl transferase (OPRT) was increased by 3.9‐fold at the protein level. These findings suggested that biochemical modulation of the 2 drugs had occurred, which was further confirmed by the results of the activity assays. These data strongly indicate that a combination chemotherapy of TXT and S‐1 is effective against gastric carcinomas and is therefore a good candidate as a standard chemotherapeutic strategy in treating these tumors. © 2006 Wiley‐Liss, Inc.
Hepatocyte growth factor activation inhibitors (HAI‐1 and HAI‐2) regulate HGF‐induced invasion of human breast cancer cells
Authors: Parr Christian , Jiang Wen G. 
Published: March 2006

AbstractHepatocyte growth factor (HGF) plays a plethora of roles in cancer metastasis and tumour growth. The interaction between tumour cells and their surrounding stromal environment is a crucial factor regulating tumour invasion and metastasis. Stromal fibroblasts are the main source of HGF in the body, and release HGF as an inactive precursor (pro‐HGF). HGF activator (HGFA), matriptase, urokinase‐type plasminogen activator and hepsin are the main factors responsible for converting pro‐HGF into active HGF. HAI‐1 and HAI‐2 are 2 novel Kunitz‐type serine protease inhibitors that regulate HGF activity through inhibition of HGFA, matriptase and hepsin action. Recent studies demonstrate that HAI‐1 and HAI‐2 may also potently inhibit a number of other pro‐metastatic serine proteases and therefore have direct bearing on the spread of tumours. Our study examined the potential of these HAI's to suppress the influence of HGF and regulate cancer metastasis. We generated a retroviral expression system that induced HAI expression in a human fibroblast cell line. Forced expression of either HAI‐1 or HAI‐2 in these fibroblasts resulted in a dramatic decrease in the production of bioactive hepatocyte growth factor (HGF). This reduction in HGF activity subsequently suppressed HGF's metastatic influence on breast cancer cells. To further assess the anti‐cancer properties of HAI‐1 and HAI‐2 we generated recombinant HAI proteins. These recombinant HAI proteins possessed the ability to potently quench HGF activity. We also demonstrate that these recombinant HAI's suppressed fibroblast‐mediated breast cancer invasion. An additional ribozyme transgenes study revealed that elimination of HAI‐1 and HAI‐2 expression, in an MDA‐MB‐231 breast cancer cell line, significantly enhanced the migratory, proliferative and invasive nature of these breast cancer cells. Overall, our data demonstrates the important roles of HAI‐1 and HAI‐2 in cancer metastasis, and reveals that these serine protease inhibitors display strong therapeutic potential. © 2006 Wiley‐Liss, Inc.