bluuebunny/crossref_metadata_2025_split huggingface dataset:
Some surprising properties of multivariate curve resolution‐alternating least squares (MCR‐ALS) algorithms
Authors: Rajkó Róbert 
Published: February 2009

AbstractIn this paper, some surprising properties are discussed related to multivariate curve resolution‐alternating least squares (MCR‐ALS) algorithms. The analytical solution of the feasible regions opens the door to follow the convergence tracks of MCR algorithms on Borgen plot at least in case of three‐component systems. Using Borgen plot, a hitherto unknown discrepancy of MCR‐ALS algorithms has been revealed, i.e. the sub‐ and even the final solutions can be outside of the range of the data matrix R. A new constraint, i.e. ‘zero orthogonal part for the estimated profiles’ for MCR‐ALS algorithms is suggested to speed up the convergence. If the minimal constraint, i.e. nonnegativity, can be only used, then the band solution should be preferred. This recommendation is strengthened by simulated investigations. However if the practical problem is simple enough, i.e. the concentration profiles are well‐separated, and/or there are no minor components, and/or the spectra are different enough, and/or there is zero range in either for concentration or spectral profiles, and/or all necessary further constraints are known and applied etc., then MCR‐ALS algorithms can work properly. Copyright © 2009 John Wiley & Sons, Ltd.
Total Syntheses of Amphidinolides B1, B4, G1, H1 and Structure Revision of Amphidinolide H2
Authors: Fürstner Alois , Bouchez Laure C. , Morency Louis , Funel Jaques‐Alexis , Liepins Vilnis , Porée François‐Hugues , Gilmour Ryan , Laurich Daniel , Beaufils Florent , Tamiya Minoru 
Published: February 2009

AbstractNature is a pretty unselective “chemist”when it comes to making the highly cytotoxic amphidinolide macrolides of the B/G/H series. To date, 16 different such compounds have been isolated, all of which could now be approached by a highly convergent and largely catalysis‐based route (see figure). This notion is exemplified by the total synthesis of five prototype members of this family.magnified imageDinoflagellates of the genusAmphidiniumproduce a “library” of closely related secondary metabolites of mixed polyketide origin, which are extremely scarce but highly promising owing to the exceptional cytotoxicity against various cancer cell lines. Because of the dense array of sensitive functionalities on their largely conserved macrocyclic frame, however, these amphidinolides of the B, D, G and H types elapsed many previous attempts at their synthesis. Described herein is a robust, convergent and hence general blueprint which allowed not only to conquest five prototype members of these series, but also holds the promise of making “non‐natural” analogues available by diverted total synthesis. This notion transpires for a synthesis‐driven structure revision of amphidinolide H2. The successful route hinges upon a highly productive Stille–Migita cross‐coupling reaction at the congested and chemically labile 1,3‐diene site present in all such targets, which required the development of a modified chloride‐ and fluoride‐free protocol. The macrocyclic ring could be formed with high efficiency and selectivity by ring‐closing metathesis (RCM) engaging a vinyl epoxide unit as one of the reaction partners. Because of the sensitivity of the targets to oxidizing and reducing conditions as well as to pH changes, the proper adjustment of the protecting group pattern for the peripheral ‐OH functions also constitutes a critical aspect, which has to converge to silyl groups only once the diene is in place. Tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF) turned out to be a sufficiently mild fluoride source to allow for the final deprotection without damaging the precious macrolides.
Molecular Editing and Biological Evaluation of Amphidinolide X and Y
Authors: Fürstner Alois , Kattnig Egmont , Kelter Gerhard , Fiebig Heinz‐Herbert 
Published: February 2009

AbstractScarce and precious: A collection of compounds with deep‐seated structural “point mutations” within the framework of the marine natural products amphidinolide X and Y was prepared by “diverted total synthesis”. The resulting products provided first insights into the cytotoxicity profile of these extremely scarce macrolides.magnified imageDeliberate deviations from the previously described total syntheses of amphidinolide X (1) and Y (2) allowed a collection of seven designed analogues of these extremely scarce marine natural products to be obtained. These fully synthetic “natural product‐like” compounds enabled first insights into the previously unknown structure–activity relationships governing this series. Although the average cytotoxicity is moderate, it was found that certain bladder, colon and prostate cancer cell lines are fairly sensitive, and that the best synthetic analogues are more active than the natural products themselves. The syntheses rely on the 9‐MeO‐9‐BBN variant of the Suzuki coupling for the formation of the carbon frameworks, as well as on Yamaguchi lactonization reactions for the cyclization of the macrocyclic rings.
Highly Enantioselective Synthesis of β‐Aminophosphinates with Two Stereogenic Atoms and Their Conversion into Optically Pure Ethyl β‐Amino‐H‐phosphinates
Authors: Zhang Dehui , Yuan Chengye 
Published: February 2009

Abstractβ‐Amino acid analogues: The nucleophilic addition of ethyl (diethoxyethyl)methylphosphinate to a variety of (S)‐(tert‐butanesulfinyl)imines leads to the isolation of two enantioenriched β‐aminophosphinates (>95 % ee; see scheme). Subsequent removal of the protecting groups through pivotal metal‐catalyzed thiophenolysis leads to optically pure ethyl β‐amino‐H‐phosphinates.magnified imageThe first highly stereoselective synthesis of β‐aminophosphinates has been realized by the nucleophilic attack of an anion generated from ethyl (1,1‐diethoxyethyl)methylphosphinate and nBuLi on (S)‐N‐(tert‐butanesulfinyl)imines at −78 °C. Subsequent removal of the protecting groups through pivotal metal‐catalyzed thiophenolysis leads to optically pure ethyl β‐amino‐H‐phosphinates. During this process, a pair of diastereoisomers with different configurations on the phosphorus atom can be obtained. Until now, Ellman N‐(tert‐butanesulfinyl)imines have demonstrated excellent chirality‐induced activity in the syntheses of both α‐aminophosphinates and β‐aminophosphinates. On the other hand, the Cram rules have been successfully applied to rationalize the highly enantioselective formation of (RC)‐α‐aminophosphinates and (RC)‐β‐aminophosphinates, whereas the phenomenon that the two pairs of diastereoisomers could both be efficiently isolated is tentatively discussed based on X‐ray crystallographic and 1H NMR spectroscopic analysis.
Cr(CO)3‐Activated Diels–Alder Reaction on Single‐Wall Carbon Nanotubes: A DFT Investigation
Authors: Nunzi Francesca , Sgamellotti Antonio , De Angelis Filippo 
Published: February 2009

AbstractBreaking barriers: In agreement with experimental evidence, it was found by means of high‐level DFT calculations that the Cr(CO)3 metal fragment considerably reduces the reaction energy barrier—for both the concerted and stepwise reaction mechanisms (see graphic)—of the Diels–Alder reaction of butadiene on (5,5) carbon nanotubes.magnified imageThe reaction mechanism and the effect of Cr(CO)3 on the Diels–Alder reaction of butadiene on (5,5) carbon nanotube sidewalls have been investigated by high‐level DFT calculations. We investigated both concerted and stepwise reaction pathways on closed‐shell and open‐shell potential‐energy surfaces. In agreement with recent experimental evidence, we found the Cr(CO)3 metal fragment to considerably reduce the reaction energy barrier, both for the concerted and stepwise reaction mechanisms. The latter mechanism, previously found to be higher in energy with traditional substrates, appears to compete with the concerted mechanism on the carbon nanotube sidewalls. An analysis of the frontier molecular orbitals on the pristine and Cr(CO)3‐complexed carbon nanotubes allowed us to identify the reason for this inverted reactivity pattern and the role of the transition metal on the addition of the diene.
Mass transfer and deodorization efficiency in a countercurrent spray tower for low superficial gas velocities
Authors: Turpin A. , Couvert A. , Laplanche A. , Paillier A. 
Published: February 2009

AbstractThe aim of this study was to characterize mass transfer and deodorization efficiency in a countercurrent spray tower for low superficial gas velocities. The influence of operating parameters (UG = 0.005 to 0.025 m s−1, UL = 6.1 × 10−5 to 2.4 × 10−4 m s−1) on the liquid retention (εL), the drop diameter (dg), the interfacial area (a) and the overall liquid and gas phase mass transfer coefficients (KLa, KGa) were estimated. The spray efficiency of some malodorous compounds was also estimated. A negative influence of the superficial gas velocity was demonstrated, during the spraying of water or chemical neutralizing scrubbing solutions. There was also an increase with the liquid flow rate. Abatements obtained were very good with respect to ammonia (>90%), and acceptable for the other compounds.
BRCA1 and BRCA2 mutations in women of different ethnicities undergoing testing for hereditary breast‐ovarian cancer
Authors: Hall Michael J. , Reid Julia E. , Burbidge Lynn A. , Pruss Dmitry , Deffenbaugh Amie M. , Frye Cynthia , Wenstrup Richard J. , Ward Brian E. , Scholl Thomas A. , Noll Walter W. 
Published: February 2009

AbstractBACKGROUND:In women at increased risk for breast and ovarian cancer, the identification of a mutation in breast cancer gene 1 (BRCA1) and BRCA2 has important implications for screening and prevention counseling. Uncertainty regarding the role of BRCA1 and BRCA2 testing in high‐risk women from diverse ancestral backgrounds exists because of variability in prevalence estimates of deleterious (disease‐associated) mutations in non‐white populations. In this study, the authors examined the prevalence of BRCA1 and BRCA2 mutations in an ethnically diverse group of women who were referred for genetic testing.METHODS:In this cross‐sectional analysis, the prevalence of BRCA1 and BRCA2 mutations was assessed in a group of non‐Ashkenazi Jewish women who underwent genetic testing.RESULTS:From 1996 to 2006, 46,276 women who met study criteria underwent DNA full‐sequence analysis of the BRCA1 and BRCA2 genes. Deleterious mutations were identified in 12.5% of women, and recurrent deleterious mutations (prevalence >2%) were identified in all ancestral groups. Women of non‐European descent were younger (mean age, 45.9 years; standard deviation [SD], 11.6 years) than European women (mean age, 50 years; SD, 11.9 years; P < .001). Women of African (15.6%; odds ratio [OR], 1.3 [95% confidence interval (95% CI), 1.1‐1.5]) and Latin American (14.8%; OR, 1.2 [95% CI, 1.1‐1.4]) ancestries had a significantly higher prevalence of deleterious BRCA1 and BRCA2 mutations compared with women of Western European ancestry (12.1%), primarily because of an increased prevalence of BRCA1 mutations in those 2 groups. Non‐European ethnicity was associated strongly with having a variant of uncertain significance; however, reclassification decreased variant reporting (from 12.8%→5.9%), and women of African ancestry experienced the largest decline (58%).CONCLUSIONS:Mutation prevalence was found to be high among women who were referred for clinical BRCA1 and BRCA2 testing, and the risk was similar across diverse ethnicities. BRCA1 and BRCA2 testing is integral to cancer risk assessment in all high‐risk women. Cancer 2009. © 2009 American Cancer Society.
Intracranial dural metastases
Authors: Nayak Lakshmi , Abrey Lauren E. , Iwamoto Fabio M. 
Published: February 2009

AbstractBACKGROUND:Intracranial dural metastases (IDM) are found at autopsy in 9% of patients with advanced systemic cancer. However, to the authors' knowledge, IDM have not been studied systematically in the modern neuroimaging era. The objective of the current study was to evaluate the demographics, clinical presentation, imaging, treatment, and prognosis of patients with IDM.METHODS:The current study was a retrospective review of 122 patients with IDM diagnosed at Memorial Sloan‐Kettering Cancer Center between 1999 and 2006. Patients with concurrent brain or leptomeningeal metastases were excluded.RESULTS:Sixty‐one percent of the patients were women; the median age at diagnosis was 59 years, the median Karnofsky performance scale (KPS) at diagnosis was 80, and the median time to IDM diagnosis from initial cancer diagnosis was 37 months. Breast (34%) and prostate (17%) cancers were the most frequent primary tumors associated with IDM. Fifty‐six percent of patients had a single dural metastasis. On imaging, 70% had metastases of the overlying skull, 44% had dural tail metastases, 53% had vasogenic edema, and 34% had brain invasion. Direct extension from skull metastases was the most common mode of spread. Eighty‐three percent of patients had active systemic disease at the time of IDM diagnosis. A lower KPS and lung cancer were associated with worse overall survival. Surgical resection and chemotherapy improved progression‐free survival, but only resection was found to be associated with improved overall survival.CONCLUSIONS:IDM affect a significant proportion of cancer patients. KPS and status of systemic cancer should guide treatment decisions. Cancer 2009. © 2009 American Cancer Society.
Patterns of disease progression in metastatic renal cell carcinoma patients treated with antivascular agents and interferon
Authors: Plimack Elizabeth R. , Tannir Nizar , Lin E , Bekele B. Nebiyou , Jonasch Eric 
Published: February 2009

AbstractBACKGROUND:The standard of care for patients with advanced renal cell carcinoma (RCC) has changed to favor targeted therapy over immunotherapy. Differences in patterns of progression between patients treated with these 2 modalities, and the impact of disease stabilization on outcome, were investigated.METHODS:Patients who progressed on first line antivascular therapy (AVT) or interferon were identified, and their medical records reviewed.RESULTS:A total of 162 patients met inclusion criteria for this analysis. Patients in the AVT group had better baseline performance status, fewer liver metastases, and more responses (CR + PR) compared with the interferon group. Both groups were equally likely to develop distant metastases; however, for patients in the AVT group, these new metastases were more likely to arise in the setting of controlled disease at baseline sites (18% vs 4%,P= .012). There was no difference in anatomic sites of progression between the 2 groups. Patients responding (CR + PR) to AVT trended toward longer progression‐free survival (PFS) compared with patients with stable disease (SD) (P= .06). No difference between responders and SD was seen in the interferon group.CONCLUSIONS:Patients with RCC treated with antivascular therapy were more likely to progress at new sites in the setting of stable disease at baseline sites, suggesting that AVT may be more effective at controlling existing sites of disease than it is at preventing new metastases. Patients with SD on AVT had shorter PFS compared with responders (CR + PR). Whether this relationship extends to overall survival requires further study. Cancer 2009. © 2009 American Cancer Society.
Central pathology review in multicenter trials and studies
Authors: Vujanić Gordan M. , Sandstedt Bengt , Kelsey Anna , Sebire Neil J. 
Published: February 2009

AbstractBACKGROUND:Central pathology review (CPR) is an important component of multicenter tumor trials. The authors retrospectively analyzed the quality of pathology material submitted to determine the benefits and limitations of rapid CPR.METHODS:Analysis of pathology specimens from previous renal tumors in children trials (1980‐2007) included the number of cases submitted, the number of slides per case, discrepancies in diagnosis and staging between institutional pathologists and CPR, and the impact of rapid CPR on treatment.RESULTS:The percentage of cases submitted for CPR increased from 76% in earlier trials to 100% in the current trial. The number of slides submitted rose from a median of 6 (International Pediatric Oncology Society [SIOP] 9301) to 25 for the SIOP‐UK Renal Tumors 2001 trial. Discrepancies between the institutional pathologists and CPR were as follows: diagnosis: SIOP 9, 17%; SIOP 93‐01, 14%; United Kingdom Wilms Tumour 3 Trial (UKWT3), 3.5%; SIOP‐UK 2001, 3.8%; staging: SIOP 6, 9%; SIOP 93‐01, 14%; UKWT3, 17%; SIOP‐UK 2001, 3.8% of cases. There were clinically significant discrepancies in diagnosis and/or stage in 30 of 152 (20%) cases submitted for delayed CPR in SIOP‐UK 2001.CONCLUSIONS:The number and quality of material submitted for CPR has markedly improved over time, predominantly due to the introduction of a simple standard operating procedure. Discrepancies in diagnosis and staging remain, but rapid review CPR allows clinicians to modify treatment if required. Benefits from the CPR system followed in SIOP‐UK 2001 have been clearly demonstrated, and similar systems should be considered for future trials of other tumors. Cancer 2009. © 2009 American Cancer Society.
The Stability of Platinum–Carbon Aerogel Catalysts upon Repeated Potential Cycles
Authors: Kim Hyun Joong , Park Hyung‐Sang , Suh Dong Jin 
Published: February 2009

AbstractA sense of stability: The stability of carbon‐supported platinum catalysts at high potentials is important for the commercialization of fuel cells for homes and cars. The electrochemical active surface (EAS) area of a Pt–C aerogel catalyst was found to increase up to 500 cycles, in contrast to that for the so‐called Tanaka catalyst which decreases with the number of repeated potential cycles.magnified image
Efficient production of androgenetic embryos by round spermatid injection
Authors: Miki Hiromi , Hirose Michiko , Ogonuki Narumi , Inoue Kimiko , Kezuka Fuyuko , Honda Arata , Mekada Kazuyuki , Hanaki Ken‐Ichi , Iwafune Hirotaka , Yoshiki Atsushi , Ishino Fumitoshi , Ogura Atsuo 
Published: February 2009

AbstractMammalian androgenetic embryos can be produced by pronuclear exchange of fertilized oocytes or by dispermic in vitro fertilization of enucleated oocytes. Here, we report a new technique for producing mouse androgenetic embryos by injection of two round spermatid nuclei into oocytes, followed by female chromosome removal. We found that injection of round spermatids resulted in high rates of oocyte survival (88%). Androgenetic embryos thus produced developed into mid‐gestation fetuses at various rates, depending on the mouse strain used. All the fetuses examined maintained paternally specific genomic imprinting memories. This technique also enabled us to produce complete heterozygous F1 embryos by injecting two spermatids from different strains. The best rate of fetal survival (12% per embryos transferred) was obtained with C57BL/6 × DBA/2 androgenetic embryos. We also generated embryonic stem cell lines efficiently with the genotype of Mus musculus domesticus × M. m. molossinus. Thus, injection of two round spermatid nuclei followed by maternal enucleation is an effective alternative method of producing androgenetic embryos that consistently develop into blastocysts and mid‐gestation fetuses. genesis 47:155–160, 2009. © 2009 Wiley‐Liss, Inc.
Malaria sporozoite antigen‐directed genome‐wide response in transgenic Drosophila
Authors: Yan Jizhou , Yang Xiang , Mortin Mark A. , Shahabuddin Mohammed 
Published: February 2009

AbstractMalaria kills a million people annually. Understanding the relationship between a causative parasite, Plasmodium falciparum, and the mosquito vector might suggest novel prevention approaches. We created and transformed into Drosophila two genes encoding, thrombospondin‐related adhesive protein (TRAP) and circumsporozoite protein (CSP), found on the cell surface of Plasmodium sporozoites. To understand a model insect's response, we induced these proteins separately and together, performing whole genome microarray analysis measuring gene expression changes. Gene ontology classification of responding genes reveals that TRAP and CSP strongly and differentially influence Drosophila genes involved with cell motility and gene regulation, respectively; however, the most striking effects are on the immune system. While immune‐related genes are but modestly elevated compared with responses to sepsis, there is a marked repression of the Toll pathway. This suggests: (1) how Plasmodium infection of the mosquito might use TRAP and CSP to modulate the host insect's physiology to promote sporozoite survival and transmission to man and (2) that approaches to elevate expression of the mosquito's Toll pathway might lead to novel methods of malaria prevention. genesis 47:196–203, 2009. © 2009 Wiley‐Liss, Inc.
Identifying genes that interact with Drosophila presenilin and amyloid precursor protein
Authors: van de Hoef Diana L. , Hughes James , Livne‐Bar Izhar , Garza Dan , Konsolaki Mary , Boulianne Gabrielle L. 
Published: February 2009

AbstractThe γ‐secretase complex is involved in cleaving transmembrane proteins such as Notch and one of the genes targeted in Alzheimer's disease known as amyloid precursor protein (APP). Presenilins function within the catalytic core of γ‐secretase, and mutated forms of presenilins were identified as causative factors in familial Alzheimer's disease. Recent studies show that in addition to Notch and APP, numerous signal transduction pathways are modulated by presenilins, including intracellular calcium signaling. Thus, presenilins appear to have diverse roles. To further understand presenilin function, we searched for Presenilin‐interacting genes in Drosophila by performing a genetic modifier screen for enhancers and suppressors of Presenilin‐dependent Notch‐related phenotypes. We identified 177 modifiers, including known members of the Notch pathway and genes involved in intracellular calcium homeostasis. We further demonstrate that 53 of these modifiers genetically interacted with APP. Characterization of these genes may provide valuable insights into Presenilin function in development and disease. genesis 47:246–260, 2009. © 2009 Wiley‐Liss, Inc.
Follistatin preferentially antagonizes activin rather than BMP signaling in Drosophila
Authors: Pentek Jozsef , Parker Louise , Wu Alison , Arora Kavita 
Published: February 2009

AbstractLigands of the transforming growth factor‐β (TGF‐β) superfamily play important roles in embryonic patterning and development throughout the animal kingdom. Consequently, extracellular factors that affect ligand stability, mobility, and receptor interaction also have profound effects on development. One such regulator, Follistatin (Fst), functions as an inhibitor of both activin and bone morphogenetic protein (BMP) subfamilies of TGF‐β ligands in vertebrates. Drosophila follistatin (fs) encodes a Fst homolog that is broadly expressed throughout development, but the in vivo function of the protein remains unclear. We show that overexpression of fs affects prepupal to pupal transition and morphogenesis, highlighting a novel requirement for TGF‐β signaling in metamorphosis. In addition, fs expression disrupts various aspects of neuronal morphogenesis, mimicking mutant phenotypes of the activin ligands, Dawdle (Daw) and Activin‐β. In assays targeting endogenous BMP signaling, we find no evidence that fs can antagonize BMP activity. We conclude that fs functions primarily as an inhibitor of activin rather than BMP ligands. genesis 47:261–273, 2009. © 2009 Wiley‐Liss, Inc.