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Search Results: 1 - 10 of 19843 matches for " Richard Strauss "
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History's Children by Anna Clark
Richard Strauss
Public History Review , 2009,
Abstract:
Complete response in gallbladder cancer to erlotinib plus gemcitabine does not require mutation of the epidermal growth factor receptor gene: a case report
Kabir Mody, Edward Strauss, Robert Lincer, Richard C Frank
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-570
Abstract: A 67 year old man with metastatic gallbladder cancer involving the liver and abdominal lymph nodes was treated with gemcitabine (1000 mg/m2) on day 1 and 8 every 21 days as well as daily erlotinib (100 mg). After four cycles of therapy, the CA 19-9 normalized and a PET/CT showed a complete remission; this response was maintained by the end of 12 cycles of therapy. Gemcitabine was then discontinued and single agent erlotinib was continued as maintenance therapy. The disease remains in good control 18 months after initiation of therapy, including 6 months on maintenance erlotinib. The only grade 3 toxicity was a typical EGFR-related skin rash. Because of the remarkable response to erlotinib plus gemcitabine, we performed tumor genotyping of the EGFR gene for response predicting mutations in exons 18, 19 and 21. This disclosed the wild-type genotype with no mutations found.This case report demonstrates a patient with stage IV gallbladder cancer who experienced a rarely encountered complete, prolonged response after treatment with an oral EGFR-TKI plus chemotherapy. This response occurred in the absence of an EGFR gene mutation. These observations should inform the design of clinical trials using EGFR-TKIs to treat gallbladder and other biliary tract cancers; such trials should not select patients based on EGFR mutation status.Biliary tract cancers (BTC) include carcinomas of the gallbladder and intra- and extra-hepatic bile ducts (cholangiocarcinomas). Gallbladder cancer is the most common type worldwide, affects women more frequently than men and is considered to be the most aggressive form of BTC with the shortest survival [1]. In contrast to cholangiocarcioma, gallbladder cancer (GBC) has a distinct molecular pathogenesis and may require a different therapeutic approach [1,2].The majority of BTC present at an advanced, incurable stage and are typically treated with chemotherapy drugs such as 5-fluoruracil, gemcitabine and cisplatin, often in combination. Response ra
The 2010 Rosetta Developers Meeting: Macromolecular Prediction and Design Meets Reproducible Publishing
P. Douglas Renfrew, Gabrielle Campbell, Charlie E. M. Strauss, Richard Bonneau
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0022431
Abstract:
Association of lipid peroxidation with hepatocellular injury in preterm infants
Barry Weinberger, Kazimierz Watorek, Richard Strauss, Gisela Witz, Mark Hiatt, Thomas Hegyi
Critical Care , 2002, DOI: 10.1186/cc1547
Abstract: Preterm infants (<35 weeks' gestation) admitted to the neonatal intensive care unit were enrolled (with their parents' informed consent) in either the 'cholestasis' group (if their direct bilirubin was >2 mg/dl [34.2 μmol/l] and duration of TPN was ≥ 10 days [n = 27]) or in the control group. Urine samples for measurement of TBARS (proportionate to lipid peroxidation) and blood specimens for analysis of serum bilirubin, ALT, AST, and alkaline phosphatase were obtained within 24 hours of enrollment.The cholestasis and control groups were comparable with respect to gestational age, birth weight, Apgar score, maximum FiO2, and duration of supplemental oxygen administration. Median serum direct bilirubin concentrations in the cholestasis and control groups were, respectively, 3.3 mg/dl (56.4 μmol/l) and 1.7 mg/dl (29.1 μmol/l) (P < 0.001). Serum ALT and AST levels were also elevated in the cholestasis group, but alkaline phosphatase levels did not differ significantly between the groups. Urinary levels of TBARS in all the infants were correlated with ALT and AST but did not differ significantly between cholestatic and control infants.Our findings suggest that oxidant stress is associated with hepatocellular injury in preterm infants. This effect is not correlated with the degree of cholestasis.The incidence of cholestasis related to total parenteral nutrition (TPN) among preterm infants has been estimated to be between 7% and 85%, depending on the population examined and the definition of cholestasis used [1]. In infants with necrotizing enterocolitis or short bowel syndrome, the prevalence of TPN-related cholestasis is 60–90% [2]. Although cholestasis is reversible in most patients after the successful advancement of enteral feeding, progressive liver fibrosis and cirrhosis occur in some patients even after complete enteral nutrition has been established [3]. Some studies have suggested that excessive amino acids, hepatotoxic bile acids, bacterial overgrowth, sepsis, m
Probing the Ionization State of the Universe at z>6
Richard L. White,Robert H. Becker,Xiaohui Fan,Michael A. Strauss
Physics , 2003, DOI: 10.1086/375547
Abstract: We present high signal-to-noise ratio Keck ESI spectra of the two quasars known to have Gunn-Peterson absorption troughs, SDSS J1030+0524 (z=6.28) and SDSS J1148+5251 (z=6.37). The Ly alpha and Ly beta troughs for SDSS J1030+0524 are very black and show no evidence for any emission over a redshift interval of ~0.2 starting at z=6. On the other hand, SDSS J1148+5251 shows a number of emission peaks in the Ly beta Gunn-Peterson trough along with a single weak peak in the Ly alpha trough. The Ly alpha emission has corresponding Ly beta emission, suggesting that it is indeed a region of lower optical depth in the intergalactic medium at z=6.08. The stronger Ly beta peaks in the spectrum of SDSS J1148+5251 could conceivably also be the result of "leaks" in the IGM, but we suggest that they are instead Ly alpha emission from an intervening galaxy at z=4.9. This hypothesis gains credence from a strong complex of C IV absorption at the same redshift and from the detection of continuum emission in the Ly alpha trough at the expected brightness. If this proposal is correct, the quasar light has probably been magnified through gravitational lensing by the intervening galaxy. The Stromgren sphere observed in the absorption spectrum of SDSS J1148+5251 is significantly smaller than expected based on its brightness, which is consistent with the hypothesis that the quasar is lensed. If our argument for lensing is correct, the optical depths derived from the troughs of SDSS J1148+5251 are only lower limits (albeit still quite strong, with tau(LyA)>16 inferred from the Ly beta trough.) The Ly beta absorption trough of SDSS J1030+0524 gives the single best measurement of the IGM transmission at z>6, with an inferred optical depth tau(LyA)>22.
Superfamily Assignments for the Yeast Proteome through Integration of Structure Prediction with the Gene Ontology
Lars Malmstr?m,Michael Riffle,Charlie E. M. Strauss,Dylan Chivian,Trisha N. Davis,Richard Bonneau,David Baker
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0050076
Abstract: Saccharomyces cerevisiae is one of the best-studied model organisms, yet the three-dimensional structure and molecular function of many yeast proteins remain unknown. Yeast proteins were parsed into 14,934 domains, and those lacking sequence similarity to proteins of known structure were folded using the Rosetta de novo structure prediction method on the World Community Grid. This structural data was integrated with process, component, and function annotations from the Saccharomyces Genome Database to assign yeast protein domains to SCOP superfamilies using a simple Bayesian approach. We have predicted the structure of 3,338 putative domains and assigned SCOP superfamily annotations to 581 of them. We have also assigned structural annotations to 7,094 predicted domains based on fold recognition and homology modeling methods. The domain predictions and structural information are available in an online database at http://rd.plos.org/10.1371_journal.pbio.?0050076_01.
Cholesterol Side-Chain Cleavage Gene Expression in Theca Cells: Augmented Transcriptional Regulation and mRNA Stability in Polycystic Ovary Syndrome
Jessica K. Wickenheisser, Jessica M. Biegler, Velen L. Nelson-DeGrave, Richard S. Legro, Jerome F. Strauss, Jan M. McAllister
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048963
Abstract: Hyperandrogenism is characteristic of women with polycystic ovary syndrome (PCOS). Ovarian theca cells isolated from PCOS follicles and maintained in long-term culture produce elevated levels of progestins and androgens compared to normal theca cells. Augmented steroid production in PCOS theca cells is associated with changes in the expression of genes for several steroidogenic enzymes, including CYP11A1, which encodes cytochrome P450 cholesterol side-chain cleavage. Here, we further examined CYP11A1 gene expression, at both the transcriptional and post-transcriptional level in normal and PCOS theca cells propagated in long-term culture utilizing quantitative RT-PCR, functional promoter analyses, and mRNA degradation studies. The minimal element(s) that conferred increased basal and cAMP-dependent CYP11A1 promoter function were determined. CYP11A1 mRNA half-life in normal and PCOS theca cells was compared. Results of these cumulative studies showed that basal and forskolin stimulated steady state CYP11A1 mRNA abundance and CYP11A1 promoter activity were increased in PCOS theca cells. Deletion analysis of the CYP11A1 promoter demonstrated that augmented promoter function in PCOS theca cells results from increased basal regulation conferred by a minimal sequence between ?160 and ?90 bp of the transcriptional start site. The transcription factor, nuclear factor 1C2, was observed to regulate basal activity of this minimal CYP11A1 element. Examination of mRNA stability in normal and PCOS theca cells demonstrated that CYP11A1 mRNA half-life increased >2-fold, from approximately 9.22+/?1.62 h in normal cells, to 22.38+/?0.92 h in PCOS cells. Forskolin treatment did not prolong CYP11A1 mRNA stability in either normal or PCOS theca cells. The 5′-UTR of CYP11A1 mRNA confers increased basal mRNA stability in PCOS cells. In conclusion, these studies show that elevated steady state CYP11A1 mRNA abundance in PCOS cells results from increased transactivation of the CYP11A1 promoter and increased CYP11A1 mRNA stability.
Superfamily Assignments for the Yeast Proteome through Integration of Structure Prediction with the Gene Ontology
Lars Malmstr?m,Michael Riffle,Charlie E. M Strauss,Dylan Chivian,Trisha N Davis,Richard Bonneau,David Baker
PLOS Biology , 2007, DOI: 10.1371/journal.pbio.0050076
Abstract: Saccharomyces cerevisiae is one of the best-studied model organisms, yet the three-dimensional structure and molecular function of many yeast proteins remain unknown. Yeast proteins were parsed into 14,934 domains, and those lacking sequence similarity to proteins of known structure were folded using the Rosetta de novo structure prediction method on the World Community Grid. This structural data was integrated with process, component, and function annotations from the Saccharomyces Genome Database to assign yeast protein domains to SCOP superfamilies using a simple Bayesian approach. We have predicted the structure of 3,338 putative domains and assigned SCOP superfamily annotations to 581 of them. We have also assigned structural annotations to 7,094 predicted domains based on fold recognition and homology modeling methods. The domain predictions and structural information are available in an online database at http://rd.plos.org/10.1371_journal.pbio.?0050076_01.
Pantothenamides Are Potent, On-Target Inhibitors of Plasmodium falciparum Growth When Serum Pantetheinase Is Inactivated
Christina Spry, Cristiano Macuamule, Zhiyang Lin, Kristopher G. Virga, Richard E. Lee, Erick Strauss, Kevin J. Saliba
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054974
Abstract: Growth of the virulent human malaria parasite Plasmodium falciparum is dependent on an extracellular supply of pantothenate (vitamin B5) and is susceptible to inhibition by pantothenate analogues that hinder pantothenate utilization. In this study, on the hunt for pantothenate analogues with increased potency relative to those reported previously, we screened a series of pantothenamides (amide analogues of pantothenate) against P. falciparum and show for the first time that analogues of this type possess antiplasmodial activity. Although the active pantothenamides in this series exhibit only modest potency under standard in vitro culture conditions, we show that the potency of pantothenamides is selectively enhanced when the parasite culture medium is pre-incubated at 37°C for a prolonged period. We present evidence that this finding is linked to the presence in Albumax II (a serum-substitute routinely used for in vitro cultivation of P. falciparum) of pantetheinase activity: the activity of an enzyme that hydrolyzes the pantothenate metabolite pantetheine, for which pantothenamides also serve as substrates. Pantetheinase activity, and thereby pantothenamide degradation, is reduced following incubation of Albumax II-containing culture medium for a prolonged period at 37°C, revealing the true, sub-micromolar potency of pantothenamides. Importantly we show that the potent antiplasmodial effect of pantothenamides is attenuated with pantothenate, consistent with the compounds inhibiting parasite proliferation specifically by inhibiting pantothenate and/or CoA utilization. Additionally, we show that the pantothenamides interact with P. falciparum pantothenate kinase, the first enzyme involved in converting pantothenate to coenzyme A. This is the first demonstration of on-target antiplasmodial pantothenate analogues with sub-micromolar potency, and highlights the potential of pantetheinase-resistant pantothenamides as antimalarial agents.
Evolution of the Ionizing Background and the Epoch of Reionization from the Spectra of z~6 Quasars
Xiaohui Fan,Vijay K. Narayanan,Michael A. Strauss,Richard L. White,Robert H. Becker,Laura Pentericci,Hans-Walter Rix
Physics , 2001, DOI: 10.1086/339030
Abstract: We study the process of cosmic reionization and estimate the ionizing background in the IGM using the Lyman series absorption in the spectra of the four quasars at 5.710^{-3} at z~6. At this redshift, the mass-averaged neutral hydrogen fraction is larger than 1%; the mildly overdense regions (delta > 3) are still mostly neutral and the comoving mean free path of ionizing photons is shorter than 8 Mpc. Comparison with simulations of cosmological reionization shows that the observed properties of the IGM at z~6 are typical of those in the era at the end of the overlap stage of reionization when the individual HII regions merge. Thus, z~6 marks the end of the reionization epoch. The redshift of reionization constrains the small scale power of the mass density fluctuations and the star forming efficiency of the first generation of objects.
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