bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Pregnanglykoside der oberirdischen Teile von Sarcostemma viminale (L.) R. Br.): Glykoside und Aglykone 307. Mitteilung
Authors: Schaub F. , Kaufmann H. , Stöcklin W. , Reichstein T.
Published: February 2011

The dried twigs and stems of Sarcostemma viminale (the climbing shrub form from South Rhodesia) contain about 1% phenolic and a similar amount of glycosidic compounds derived from 2‐deoxysugars; only traces of cardenolides are present. After mild acidic hydrolysis 5 sugars could be detected and subsequently isolated in pure form. Three of them (d‐cymarose, d‐digitoxose and lilacinobiose) were obtained crystalline, the two others (d‐oleandrose and viminose) in amorphous form. Viminose is a new sugar, a disaccharide which contains d‐thevetose, and d‐Digitoxose at the reducing end [30 b].

The mixture of aglycones, obtained after mild acidic hydrolysis, contained mainly five components (F, G, H. J and K), all of which could be isolated in pure form. F, G and J were crystalline. F was identified as metaplexigenin (1), J as mono‐O‐acetyl‐mono‐O‐benzoyl‐sarcostin (5) and K as 12,20‐di‐O‐benzoyl‐sarcostin (6). G and H are new compounds whose structures (G = 12‐O‐benzoyl‐deacetyl‐metaplexigenin (2), H = di‐O‐benzoyl‐viminolone (3)) are deduced in the following paper. After alkaline hydrolysis of the aglycone mixture, sarcostin, deacetylmetaplexigenin and small amounts of lineolon could be dedected by paper‐ and thinlayerchromatography.

The two pregnane derivatives EA‐42 and EA‐43 described by Abisch et al. [21] could be identified with 3, 20‐di‐O‐benzoyl‐utendin and 3, 20‐di‐O‐benzoyl‐sarcostin, respectively.

In the NMR.‐spectra of sarcostin and of many (not all) of its derivatives a strong signal (mostly a singlet corresponding to ca. 3 protons at ca. δ = 2 ppm) is present, which cannot be explained with the suggested structures. The cause of this extra signal could not be elucidated.
Die Struktur der Genine G (12‐O‐Benzoyl‐desacetylmetaplexigenin) und H (Di‐O‐benzoyl‐viminolon) aus den Stengeln von Sarcostemma viminale (L.) R.Br.: Glykoside und Aglykone 308. Mitteilung
Authors: Schaub F. , Stöcklin W. , Relchstein T.
Published: February 2011

The following structures for the two new genins G and H from Sarcostemma viminale have been deduced. Genin G is shown to be 12‐O‐benzoyl‐deacetylmetaplcxigenin (3). On the basis of physical data, its behaviour in KOH‐methanol solution and its positive test with alcaline silver‐diammine solution, the structure of 3β, 8β, 14β, 17β‐tetrahydroxy‐12β, 21‐dibenzoyloxy‐20‐oxo‐17α‐pregn‐5‐ene (4) is proposed for genin H. This substance therefore contains a dihydroxyacetone group like some corticoids (e.g. Cortisol), but with different stereochemistry at C‐14 and C‐17.
Photochemische Reaktionen: 46. Mitteilung [1]: Zur Photochemie von α,β‐ungesättigten γ‐Aldehydoketonen I. Die UV.‐Bestrahlung von 3,19‐Dioxo‐17β‐acetoxy‐Δ4‐androsten
Authors: Pfenninger E. , Poel D. E. , Berse C. , Wehrli H. , Schaffner K. , Jeger O.
Published: February 2011

Irradiation of 3,19‐dioxo‐17β‐acetoxy‐Δ4‐androstene (2) at room temperature in either of its two absorption bands centered at about 245 and 315 nm, respectively, led to products 21, 22, and 23 (Chart 3). Compounds 21 and 22 result from rearrangements involving intramolecular formal 1,2‐ (→21) and 1,3‐shifts (→22) of the angular formyl group, and the formation of compound 23 proceeds through the elimination of the formyl radical and the incorporation of a hydrogen from the medium. Evidence favors the latter process to be a secondary radical reaction rather than a primary photochemical step.
Protonenresonanz‐Spektren des CycIohexa‐3,5‐dien‐1‐on‐Systems (ortho‐Dienone)
Authors: Regel W. , Von Philipsborn W.
Published: February 2011

Proton magnetic resonance spectra of a scries of ortho‐dienones have been analyzed using multiple resonance and computer techniques. The sequence of the chemical shifts are in agreement with the calculated π‐electron distribution. The coupling constants of the ring protons are of like sign, whereas those of the methyl protons with the ring protons alternate in sign with the number of intervening bonds.
Abbau von Polypeptid‐Metall‐Komplexen VI.) Abbau des Ni2+‐Angiotensin‐II‐Komplexes durch H2O2
Authors: Ch. Curtius H. , Anders P. , Erlenmeyer H. , Sigel H.
Published: February 2011

After degradation of the Ni2+ complex of val5‐angiotensin II‐asp1‐β‐amid by H2O2 the peptide fragments were separated by high voltage electrophoresis and by ion exchange. The fragments were hydrolyzed and the amino acids determined by the method of Stein & Moore.
Sur l'acylation des méthylfluorènes III [1]: Benzoylation et acétylation du méthyl‐3‐fluorène
Authors: Chardonnens Louis , Dousse Roland
Published: February 2011

Benzoylation and acétylation of 3‐methyl‐fluorene according to Friedel‐Crafts in carbon disulfide with aluminium chloride yielded the corresponding 2‐acyl derivatives. By oxidation the benzoyl derivative gave 2‐benzoyl‐9‐oxo‐fluorene‐3‐carboxylic acid, cychsable into the known 2,3‐phthalyl‐fluorenone. By Clemmensen reduction, the acetyl derivative gave 3‐methyl‐2‐ethyl‐fluorene.
Reaktionen von niederwertigen Di‐cyclopentadienyl‐titan‐Verbindungen mit Sauerstoff und Stickstoffmonoxid
Authors: Salzmann J.‐J
Published: February 2011

The reactions of di‐cyclpentadienyl‐titanium and di‐cyclopentadienyl‐di‐carbonyl‐titanium with oxygen lead to polymeric di‐cyclopentadienyl‐peroxo‐titanium. The reaction of di‐cyclopentadienyl‐titanium with nitrogen oxide gives a polymeric hyponitrit‐titanium compound. Both derivatives have been investigated by infrared spectra and gaschromatography.
Elektrolytische Desoxydation von Kupferschmelzen
Authors: Korousic B. , Marincek B.
Published: February 2011

Durch elektrolytische Desoxydation konnte der Sauerstoffgehalt von Kupferschmelzen auf etwa 7–10 ppm gesenkt werden.
Zur Kinetik des durch Cu2+‐Äthylendiamin katalysierten H2O2‐Zerfalls: Metallionen und H2O2, 14. Mitteilung
Authors: Kaden Thomas , Sigel Helmut
Published: February 2011

Kinetic studies of the Cu2+‐ethylenediamine catalysed decomposition of H2O2 show the initial rate v0 of H2O2 decomposition to be proportional to [H+]−1, [H2O2], and [Cu2+‐en]2. Maximal velocity is found at a ratio of [Cu2+]tot:[en]tot = 1:1,5. It is suggested that the active complex has a binuclear structure. This structure and probable mechanisms of the reaction are discussed. The kinetic measurements of the Cu2+‐diethylenetriamine‐H2O2 system are difficult to interprete because of degradation of the ligand by H2O2.
Beiträge zur Chemie der Si‐N‐Bindung, XII Cyclodisilazan‐Polymere
Authors: Fink Walter
Published: February 2011

Cyclodisilazan‐Polymere der Formeln

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werden A) durch die Pyrolyse von N,N'‐Diorganosdandiaminen mit aromatischen Diaminen sowie durch die katalytische Silylierung von aroniatischen und aliphatischen Draminen mit Silanen RnSiH4−n (n = 1 und 2), und B) durch die Reaktion von α,ω‐diorgano‐aminosilyl‐substituierten monomeren bis oligomeren Cyclodisilazanen mit Bisphenolen und difunktionellen Silanolen dargestellt. Über die physikahschen Eigenschaften dieser Polymeren wird berichtet.
A phase I study of vaccination with NY‐ESO‐1f peptide mixed with Picibanil OK‐432 and Montanide ISA‐51 in patients with cancers expressing the NY‐ESO‐1 antigen
Authors: Kakimi Kazuhiro , Isobe Midori , Uenaka Akiko , Wada Hisashi , Sato Eiichi , Doki Yuichiro , Nakajima Jun , Seto Yasuyuki , Yamatsuji Tomoki , Naomoto Yoshio , Shiraishi Kenshiro , Takigawa Nagio , Kiura Katsuyuki , Tsuji Kazuhide , Iwatsuki Keiji , Oka Mikio , Pan Linda , Hoffman Eric W. , Old Lloyd J. , Nakayama Eiichi
Published: February 2011

We conducted a phase I clinical trial of a cancer vaccine using a 20‐mer NY‐ESO‐1f peptide (NY‐ESO‐1 91–110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 μg of NY‐ESO‐1f peptide mixed with 0.2 KE Picibanil OK‐432 and 1.25 ml Montanide ISA‐51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY‐ESO‐1f peptide vaccine was well tolerated. Vaccine‐related adverse events observed were fever (Grade 1), injection‐site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY‐ESO‐1f peptide resulted in an increase or induction of NY‐ESO‐1 antibody responses in nine of ten patients. The sera reacted with recombinant NY‐ESO‐1 whole protein as well as the NY‐ESO‐1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine‐induced CD4 and CD8 T cells responded to NY‐ESO‐1 91–108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20‐mer NY‐ESO‐1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY‐ESO‐1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients.
Male circumcision and anatomic sites of penile high‐risk human papillomavirus in Rakai, Uganda
Authors: Tobian Aaron A.R. , Kong Xiangrong , Gravitt Patti E. , Eaton Kevin P. , Kigozi Godfrey , Serwadda David , Oliver Amy E. , Nalugoda Fred , Makumbi Frederick , Chen Michael Z. , Wawer Maria J. , Quinn Thomas C. , Gray Ronald H.
Published: February 2011

Male circumcision (MC) reduces penile high‐risk human papillomavirus (HR‐HPV) on the coronal sulcus and urethra. HR‐HPV varies by anatomic site, and it is unknown whether MC decreases HR‐HPV on the penile shaft. We assessed the efficacy of MC to reduce HR‐HPV on the penile shaft and compared it to known efficacy of MC to reduce HR‐HPV on the coronal sulcus. HIV‐negative men randomized to receive immediate circumcision (intervention) or circumcision delayed for 24 months (control) were evaluated for HR‐HPV at 12 months postenrollment using the Roche HPV Linear Array assay. Among swabs with detectable β‐globin or HPV, year 1 HR‐HPV prevalence on the coronal sulcus was 21.5% in the intervention arm and 36.3% in the control arm men [adjusted prevalence risk ratios (PRRs) = 0.57, 95% CI 0.39–0.84, p = 0.005]. On the shaft, year 1 HR‐HPV prevalence was 15.5% in the intervention and 23.8% in the control arm (adjusted PRR = 0.66, 95% CI 0.39–1.12, p = 0.12). Efficacy of MC to reduce HR‐HPV on the shaft was similar to efficacy on the coronal sulcus (p = 0.52). In a sensitivity analysis in which swabs without detectable β‐globin or HPV were included as HPV negative, prevalence of HR‐HPV on the shaft was lower in the intervention arm (7.8%) than control arm (13.6%; PRR 0.57, 95% CI 0.33–0.99, p < 0.05). HR‐HPV was more frequently detected on the coronal sulcus than penile shaft among uncircumcised men (36.3% vs. 23.8%, respectively, p = 0.02) and circumcised men (21.5% vs. 15.5%, respectively, p = 0.24). MC reduced HR‐HPV prevalence on both the coronal sulcus and shaft.
Downregulation of breast cancer resistance protein in colon adenomas reduces cellular xenobiotic resistance and leads to accumulation of a food‐derived carcinogen
Authors: Dietrich Christoph G. , Vehr Ann‐Kathrin , Martin Ina V. , Gaßler Nikolaus , Rath Timo , Roeb Elke , Schmitt Johannes , Trautwein Christian , Geier Andreas
Published: February 2011

Several molecular changes in colorectal adenomas provide the basis of the adenoma–carcinoma sequence. We investigated the expression of xenobiotic ATP‐binding cassette (ABC) transporters in humans and in ApcMin mice and conducted functional studies estimating the importance of the expression changes. Twenty‐nine adenomas from 21 patients and eight adenomas from four ApcMin mice were analyzed using Western blotting and quantitative Real‐time polymerase chain reaction (RT‐PCR). Adjacent healthy tissue served as control for each polyp. Breast cancer resistance protein (BCRP) was significantly downregulated in human colorectal adenomas (to 28 ± 35% of adjacent healthy tissue). This was in line with data from ApcMin mice adenomas, where downregulation was significant as well (to 58 ± 34%). In parallel, quantitative RT‐PCR showed BCRP mRNA downregulation in human adenomas (to 17 ± 31%). Basal multidrug resistance‐associated protein 2 expression was low and did not change in adenomas; multidrug resistance transporter 1 expression also did not differ between adenomas and healthy tissue. In a functional study, ApcMin mice received radioactively labelled 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐β] pyridine (PhIP), a food colon carcinogen and substrate of BCRP, by oral gavage with analysis of PhIP accumulation and DNA adduct formation 48 hr later. In this setting, we could demonstrate a higher carcinogen concentration in adenomas of ApcMin mice (181 ± 113% of normal tissue) including immunohistochemical detection of PhIP–DNA adducts. We conclude that significant transcriptional downregulation of BCRP/Bcrp leads to higher carcinogen concentrations in colorectal adenomas of mice and men. This might promote the adenoma–carcinoma sequence by higher genotoxic effects. The results indicate a possible role of transporter deficiencies in susceptibility for colon carcinoma.
Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case–control study
Authors: Urayama Kevin Y. , Holcatova Ivana , Janout Vladimir , Foretova Lenka , Fabianova Eleonora , Adamcakova Zora , Ryska Miroslav , Martinek Arnost , Shonova Olga , Brennan Paul , Scélo Ghislaine
Published: February 2011

The relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596 frequency‐matched controls from the Czech Republic and Slovakia enrolled between 2004 and 2009. Analyses using multivariable logistic regression showed an increased risk of pancreatic cancer associated with elevated quartiles of BMI at ages 20 [fourth quartile: odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.23, 2.61] and 40 (fourth quartile: OR = 1.57, 95% CI: 1.09, 2.27) compared to the lowest quartile. Consistent results were observed for body size score at ages 20 (high versus low: OR = 1.66, 95% CI: 1.08, 2.57) and 40 (medium versus low: OR = 1.36, 95% CI: 1.00, 1.86), but no association was found for BMI and body size score at 2 years before the interview. Stronger risk estimates for BMI were observed in males than females, particularly at age 20, but the analysis of body size yielded similar estimates by sex. When considering excess body weight at both ages 20 and 40 jointly, the highest risk estimates were observed among subjects with elevated levels at both time periods in the analysis of BMI (OR = 1.86, 95% CI: 1.32, 2.62) and body size (OR = 1.53, 95% CI: 1.09, 2.13). These findings, based on two different measures, provide strong support for an increased risk of pancreatic cancer associated with excess body weight, possibly strongest during early adulthood.
Costimulation by chimeric antigen receptors revisited the T cell antitumor response benefits from combined CD28‐OX40 signalling
Authors: Hombach Andreas A. , Abken Hinrich
Published: February 2011

The therapeutic success of adoptive therapy with chimeric antigen receptor (CAR) engineered T cells depends on the appropriate costimulation of CD3ζ to induce full T cell activation. Costimulatory endodomains of the CD28 family are therefore fused with CD3ζ in a dual signalling CAR. Serious adverse events in two most recent trials; however, highlight the need to analyse in more detail the impact of each costimulatory endodomain on individual effector functions of redirected T cells. We therefore performed a thoroughly controlled side‐by‐side comparison of the most frequently used endodomains with respect to their impact on CD4+ and CD8+ T cell effector functions. CD28 reinforced T cell proliferation and is mandatory to induce IL‐2. In the absence of added IL‐2, CD28 and OX40 (CD137) but not 4‐1BB (CD134) enhanced specific cytolysis. While CD28, 4‐1BB and OX40 similarly improved pro‐inflammatory cytokine secretion, OX40 most efficiently prevented activation induced cell death of CD62L− effector memory T cells. CD28 was superior to initiate the T cell response, OX40 and 4‐1BB sustained the response in long term with OX40 being most effective. We consequently combined the beneficial functions in a 3rd generation CD28‐OX40 CAR which substantially improved the antitumor response without loosing specificity.
The activated transforming growth factor‐beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer
Authors: Yamamura Shogo , Matsumura Noriomi , Mandai Masaki , Huang Zhiqing , Oura Tomonori , Baba Tsukasa , Hamanishi Junzo , Yamaguchi Ken , Kang Hyun Sook , Okamoto Takako , Abiko Kaoru , Mori Seiichi , Murphy Susan K. , Konishi Ikuo
Published: February 2011

Peritoneal dissemination including omental metastasis is the most frequent route of metastasis and an important prognostic factor in advanced ovarian cancer. We analyzed the publicly available microarray dataset (GSE2109) using binary regression and found that the transforming growth factor (TGF)‐beta signaling pathway was activated in omental metastases as compared to primary sites of disease. Immunohistochemical analysis of TGF‐beta receptor type 2 and phosphorylated SMAD2 indicated that both were upregulated in omental metastases as compared to primary disease sites. Treatment of the mouse ovarian cancer cell line HM‐1 with recombinant TGF‐β1 promoted invasiveness, cell motility and cell attachment while these were suppressed by treatment with A‐83‐01, an inhibitor of the TGF‐β signaling pathway. Microarray analysis of HM‐1 cells treated with TGF‐β1 and/or A‐83‐01 revealed that A‐83‐01 efficiently inhibited transcriptional changes that are induced by TGF‐β1. Using gene set enrichment analysis, we found that genes upregulated by TGF‐β1 in HM‐1 cells were also significantly upregulated in omental metastases compared to primary sites in the human ovarian cancer dataset, GSE2109 (false discovery rate (FDR) q = 0.086). Therapeutic effects of A‐83‐01 in a mouse model of peritoneal dissemination were examined. Intraperitoneal injection of A‐83‐01 (150 μg given three times weekly) significantly improved survival (p = 0.015). In summary, these results show that the activated TGF‐β signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer.
VEGFR‐2 expression in human melanoma: Revised assessment
Authors: Molhoek Kerrington R. , Erdag Gulsun , Rasamny Jk , Murphy Cheryl , Deacon Donna , Patterson James W. , Slingluff Craig L. , Brautigan David L.
Published: February 2011

Vascular endothelial growth factor (VEGF) is an angiogenic factor that also functions as an autocrine growth factor for VEGF receptor (VEGFR)‐2+ melanomas. In multiple studies, VEGFR‐2 was detected by immunostaining in 78–89% of human melanoma cells, suggesting that most patients with melanoma would benefit from anti‐VEGF therapy. Here, we evaluated 167 human melanoma specimens in a tissue microarray to verify the presence of VEGFR‐2, but found disparities in staining with commercial antibodies A‐3 and 55B11. Antibody A‐3 stained melanoma cells in 79% of specimens, consistent with published results; however, we noted extensive nonspecific staining of other cells such as smooth muscle and histiocytes. In contrast, antibody 55B11 stained melanoma cells in only 7% (95% confidence interval: 3.3–11.5) of specimens. As an internal positive control for VEGFR‐2 detection, vascular endothelial cells were stained with antibody 55B11 in all specimens. We compared VEGFR‐2+ and VEGFR‐2− melanoma cell lines by immunoblotting and immunohistochemistry after small interfering RNA (siRNA) knockdown and transient overexpression of VEGFR‐2 to validate antibody specificity. Immunoblotting revealed that A‐3 primarily cross‐reacted with several proteins in both cell lines and these were unaffected by siRNA knockdown of VEGFR‐2. In contrast, 55B11 staining of VEGFR‐2+ cells was mostly eliminated by siRNA knockdown of VEGFR‐2 and increased in VEGFR‐2− melanoma cell lines following transfection to express ectopic VEGFR‐2. Our results show that relatively few melanoma cells (<10%) express detectable levels of VEGFR‐2, and therefore, the majority of patients with melanoma are unlikely to benefit from antiproliferative effects of anti‐VEGF therapy.
Functional interrelationship between the WASF3 and KISS1 metastasis‐associated genes in breast cancer cells
Authors: Teng Yong , Liu Mingyao , Cowell John K.
Published: February 2011

Loss of WASF3 function in breast cancer cells results in loss of invasion phenotypes and reduced metastatic potential. By using oligonucleotide arrays, we now demonstrate that knockdown of WASF3 leads to the upregulation of the KISS1 metastasis suppressor gene with concomitant reduced invasion and loss of matrix metalloproteinases (MMP)‐9 activity. Using a luciferase reporter, KISS1 transcription is significantly increased in the absence of WASF3. Knockdown of KISS1 in WASF3‐silenced cells resulted in the recovery of the invasion phenotype. WASF3 knockdown also resulted in elevated IκBα levels in the cytoplasm and reduced levels of nuclear factor‐kappa‐B (NF‐κB) p65/50 subunits in the nucleus. Tumor necrosis factor‐alpha (TNF‐α) has been associated with cell invasion through induction of MMP‐9 production via KISS1 regulation of the NF‐κB pathway. When WASF3 knockdown cells are treated with TNF‐α, no effect is seen on invasion or nuclear translocation of NF‐κB. Thus, coordinated expression patterns of the WASF3 metastasis promoter gene and the KISS1 metastasis suppressor gene appear to exert their influence through inhibition of NF‐κB signaling, which in turn regulates MMP‐9 production facilitating invasion.
Bezielle (BZL101)‐induced oxidative stress damage followed by redistribution of metabolic fluxes in breast cancer cells: A combined proteomic and metabolomic study
Authors: Klawitter Jelena , Klawitter Jost , Gurshtein Jennifer , Corby Kyler , Fong Sylvia , Tagliaferri Mary , Quattrochi Linda , Cohen Isaac , Shtivelman Emma , Christians Uwe
Published: February 2011

Bezielle is an orally administered aqueous extract of Scutellaria barbata for treatment of advanced and metastatic breast cancer. Phase I trials showed promising tolerability and efficacy. In our study, we used a combined proteomic–metabolomic approach to investigate the molecular pathways affected by Bezielle in ER‐positive BT474 and ER‐negative SKBR3 cell lines. In both, Bezielle inhibited cell proliferation, induced cell death and G2 cycle arrest by regulating the mediator proteins Jab1, p27Kip1 and p21Cip1. In addition, it stimulated reactive oxygen species production, hyperactivation of PARP and inhibition of glycolysis. Bezielle's ability to induce oxidative stress was associated with the changes in expression of redox potential maintaining enzymes: glutathione‐ and thioredoxin‐related proteins and peroxiredoxins. In regards to cell metabolism, decreased expression of α‐enolase was associated with a reduction of de novo
13C‐lactate formation. Reduced Krebs cycle activity as evidenced by the reduced expression of α‐ketoglutarate dehydrogenase and succinyl‐CoA synthetase led to decreased intracellular succinate concentrations. By inhibiting glucose metabolism, cells reacted by lowering the expression of glucose transporters and resulting in decreased intracellular glucose concentration. Decreased expression of fatty acid synthase and reduced concentration of phosphocholine indicated considerable changes in phospholipid metabolism. Ultimately, by inhibiting the major energy‐producing pathways, Bezielle caused depletion of ATP and NAD(H). Both cell lines were responsive, thus suggesting that Bezielle has the potential to be effective against ER‐negative breast cancers. In conclusion, Bezielle's cytotoxicity toward cancer cells is primarily based on inhibition of metabolic pathways that are preferentially activated in tumor cells thus explaining its specificity for cancer cells.
Comparison of visual inspection with acetic acid and cervical cytology to detect high‐grade cervical neoplasia among HIV‐infected women in India
Authors: Sahasrabuddhe Vikrant V. , Bhosale Ramesh A. , Kavatkar Anita N. , Nagwanshi Chandraprabha A. , Joshi Smita N. , Jenkins Cathy A. , Shepherd Bryan E. , Kelkar Rohini S. , Sahay Seema , Risbud Arun R. , Vermund Sten H. , Mehendale Sanjay M.
Published: February 2011

Human immunodeficiency virus (HIV)‐infected women in India and other developing country settings are living longer on antiretroviral therapy, yet their risk for human papillomavirus (HPV)‐induced cervical cancer remains unabated because of lack of cost‐effective and accurate secondary prevention methods. Visual inspection after application of dilute acetic acid on the cervix (VIA) has not been adequately studied against the current standard: conventional cervical cytology (Pap smears) among HIV‐infected women. We evaluated 303 nonpregnant HIV‐infected women in Pune, India, by simultaneous and independent screening with VIA and cervical cytology with disease ascertainment by colposcopy and histopathology. At the cervical intraepithelial neoplasia (CIN2+) disease threshold, the sensitivity, specificity and positive and negative predictive value estimates of VIA were 80, 82.6, 47.6 and 95.4% respectively, compared to 60.5, 59.6, 22.4 and 88.7% for the atypical squamous cells of undetermined significance or severe (ASCUS+) cutoff on cytology, 60.5, 64.6, 24.8 and 89.4% for the low‐grade squamous intraepithelial cells or severe (LSIL+) cutoff on cytology and 20.9, 96.0, 50.0 and 86.3% for high‐grade squamous intraepithelial lesion or severe (HSIL+) cutoff on cytology. A similar pattern of results was found for women with the presence of carcinogenic HPV‐positive CIN2+ disease, as well as for women with CD4+ cell counts <200 and <350 μL−1. Overall, VIA performed better than cytology in this study with biologically rigorous endpoints and without verification bias, suggesting that VIA is a practical and useful alternative or adjunctive screening test for HIV‐infected women. Implementing VIA‐based screening within HIV/acquired immunodeficiency syndrome care programs may provide an easy and practical means of complementing the highly anticipated low‐cost HPV‐based rapid screening tests in the near future, thereby contributing to improve program effectiveness of screening.
Induction of autophagy promotes differentiation of glioma‐initiating cells and their radiosensitivity
Authors: Zhuang Wenzhuo , Li Bingzong , Long Linmei , Chen Liesong , Huang Qiang , Liang Zhongqin
Published: February 2011

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by increased proliferation and resistance to chemotherapy and radiotherapy. Recently, the identification of tumor‐initiating cells with stem‐like properties in diverse human cancers including GBM represents an important conceptual advance in cancer biology with therapeutic implications. However, the factors determining the differential development and radiosensitization of glioma‐initiating cells (GICs) remain poorly defined. Here, we report that rapamycin induced differentiation of GICs and increased their sensitivity to radiation by activating autophagy. Transient in vitro exposure to rapamycin and radiation abolished the capacity of transplanted GICs to establish intracerebral GBMs. Most importantly, in vivo combination of rapamycin and radiation effectively blocked the tumor growth and associated mortality that occurs in mice after intracerebral grafting of human GICs. We demonstrate that rapamycin activated their autophagy and triggers the differentiation cascade in GICs isolated from human GBMs. This was followed by a reduction in proliferation, cell viability, clonogenic ability and increased expression of neural differentiation markers after radiation. Our results suggest that autophagy plays an essential role in the regulation of self‐renewal, differentiation, tumorigenic potential and radiosensitization of GICs, suggesting autophagy could be a promising therapeutic target in a subset of GBMs. We propose that autophagy defect in GICs contributes to radioresistance of GICs by desensitizing GICs to normal differentiation cues. Activating autophagy may abrogate the resistance of GICs to radiation and could lead to the development of novel therapeutic approaches for the treatment of GBMs.
Fetal exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin induces expression of the chemokine genes Cxcl4 and Cxcl7 in the perinatal mouse brain
Authors: Mitsui Tetsuo , Taniguchi Naofumi , Kawasaki Nobuchika , Kagami Yoshihiro , Arita Jun
Published: February 2011

Fetal exposure to dioxins affects brain development and influences behaviors in human and laboratory animals. However, the cellular target and mechanisms of the neurotoxic action of dioxins are largely unknown. To investigate the molecular basis for the neurotoxicity of dioxins, pregnant C57BL/6 mice were exposed to 5 µg kg−1 body weight of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) by a single gavage on gestational day 12.5 (GD 12.5), and gene expression of the whole fetal brain at GD 18.5 was profiled by DNA microarray analysis. The analysis revealed that the expression of two chemokine genes, Cxcl4 and Cxcl7, was up‐regulated by TCDD exposure. Real‐time PCR analysis verified that they were up‐regulated by TCDD in both male and female brains, while the mRNA levels of a majority of other chemokines and their receptor genes were not affected. The up‐regulation was TCDD dose‐dependent and peaked at GD 15.5–18.5. In situ hybridization analysis showed that the Cxcl4 mRNA expression was localized in part of the surface of cerebral cortex and that the level was increased by TCDD treatment. These results suggest that Cxcl4 and Cxcl7 play a role in the development of neurobehavioral alterations that are triggered by in utero TCDD exposure and later surface in adults. Copyright © 2011 John Wiley & Sons, Ltd.
A tabular source approach to modelling and simulating device and circuit noise in the time domain
Authors: Brinson M. E. , Jahn S. , Nabijou H.
Published: February 2011

Simulation of device and circuit noise at low frequencies is often carried out as part of a small‐signal ac analysis. Moreover, circuit simulators with rf analysis capabilities usually specify circuit performance in terms of S parameters and model high‐frequency noise in terms of noise waves and correlation matrices. It is also unusual to find circuit simulators that extend noise simulation to the time domain. This is particularly true for software packages developed from SPICE 2g6 or 3f5. This paper introduces a simple tabular noise source technique, which adds time‐domain noise to semiconductor device models and integrated circuit macromodels. The proposed technique is suitable for use with any general purpose circuit simulator. To demonstrate the power of the suggested approach the text describes time‐domain noise extensions to the SPICE diode, BJT, JFET, MOSFET and MESFET models. These noise extensions have been implemented and tested with the ‘Quite universal circuit simulator’ (Qucs). Copyright © 2011 John Wiley & Sons, Ltd.
Promoting group potency in project teams: The importance of group identification
Authors: Lee Cynthia , Farh Jiing‐Lih , Chen Zhi‐Jun
Published: February 2011

We examined the antecedents and consequences of group potency in 71 multinational project teams in the Greater China region. We extended the theoretical basis of group potency by employing group identification theory. Results showed that group identification was one of the key factors in developing group potency. Further, fostering the acceptance of group goals that are interdependent was important for increasing group identification. We discuss the implications of our findings for future research. Copyright © 2011 John Wiley & Sons, Ltd.
Shell bed tempestites in the Chenier Plain of Louisiana: late Holocene example and modern analogue
Authors: Williams Harry F.L.
Published: February 2011

Hurricane Ike's storm surge deposited a concentrated shell bed in the form of a series of coalescing washover fans over backshore sand and adjoining marshland in part of southwest Louisiana's Chenier Plain. The shell bed is a tempestite and has distinctive morphological, sedimentological and biogenic characteristics that provide a modern analogue to aid interpretation of older shell bed tempestites in the geological record. The shell bed has a wedge‐shaped profile that thickens landward, is about 40 m wide, up to 27 cm thick and extends several hundred metres parallel to the shore. Shells are predominantly disarticulated valves of the common bivalve Mulinia lateralis, probably reworked and transported landward from skeletal remains offshore. The shell bed has an erosional base, is bioclast supported, normally graded and has common mud rip‐up clasts. Similarities between the modern shell bed and another concentrated shell deposit, forming part of a sandy beach ridge some 1.5 km inland, suggest that the palaeo shell deposit is also a tempestite recording hurricane washover of a former shoreline 600 a ago. These findings demonstrate that the shell bed deposited by Hurricane Ike is a valuable analogue for palaeotempestological investigations and that hurricanes have likely contributed to the construction of both modern berm ridges and palaeo beach ridges on this coastal plain. Copyright © 2011 John Wiley & Sons, Ltd.
SERS activity of pulsed laser ablated silver thin films with controlled nanostructure
Authors: Fazio E. , Neri F. , D'Andrea C. , Ossi P. M. , Santo N. , Trusso S.
Published: February 2011

The surface‐enhanced Raman scattering (SERS) activity of silver thin films deposited by the pulsed laser ablation technique was investigated. The samples were grown in a controlled Ar atmosphere at pressures ranging between 10 and 70 Pa, and changing the number of laser pulses. Different surface morphologies, from isolated nearly spherical nanoparticles (NPs) to larger islands with smooth edges, were observed by means of scanning and transmission electron microscopies, as a function of the different deposition conditions adopted. SERS measurements were performed by soaking the samples in rhodamine 6G aqueous solutions over the concentration range between 1.0 × 10−4 and 5.0 × 10−8 M. Raman spectra were acquired using both the 632.8 and 514.5 nm excitation sources. The dependence of the SERS activity of the samples on the observed surface morphology is presented and discussed. The presence of the so called hot spots is envisaged. Copyright © 2011 John Wiley & Sons, Ltd.
Deployment to a combat zone and other risk factors for mental health‐related disability discharge from the U.S. Army: 1994–2007
Authors: Bell Nicole S. , R.Hunt Phillip , Harford Thomas C. , Kay Ashley
Published: February 2011

Combat exposure is associated with subsequent mental health symptoms, but progression to mental health disability is unclear. Army soldiers discharged with mental health disability (n = 4,457) were compared to two matched control groups: other disability discharge (n = 8,974) and routine discharge (n = 9,128). In multivariate logistic models, odds of mental health disability discharge versus other disability and routine discharge were significantly higher for soldiers deployed to combat zones; odds ratios increased with deployment time. Prior mental health hospitalization decreased these odds, though they remained significantly elevated. Mental health hospitalization with successful treatment may facilitate better coping during deployment. The frequency of disability after mental health hospitalization suggests remaining gaps in deployment‐related mental health assessment and treatment.
Anilinolysis of reactive aryl 2,4‐dinitrophenyl carbonates: Kinetics and mechanism
Authors: Castro Enrique A. , Domecq Claudia , Santos José G.
Published: February 2011

The reactions of a series of anilines with phenyl 2,4‐dinitrophenyl (1), 4‐nitrophenyl 2,4‐dinitrophenyl (2), and bis(2,4‐dinitrophenyl) (3) carbonates are subjected to a kinetic investigation in 44 wt% ethanol–water, at 25.0 ± 0.1°C and an ionic strength of 0.2 M. Under amine excess pseudo‐first‐order rate coefficients (kobs) are obtained. Plots of kobs against free amine concentration at constant pH are linear, with slopes kN. The Brønsted plots (log kN vs. anilinium pKa) for the anilinolysis of 1–3 are linear, with slope (β) values of 0.52, 0.61, and 0.63, respectively. The values of these slopes and other considerations suggest that these reactions are ruled by a concerted mechanism. For these reactions, the kN values follow the reactivity sequence: 3 > 2 > 1. Namely, the reactivity increases as the number of nitro groups attached to the nonleaving group increases. Comparison of the reactions of this work with the stepwise pyridinolysis of carbonates 1–3 indicates that the zwitterionic tetrahedral intermediate (T±) formed in the pyridinolysis reactions is destabilized by the change of its pyridino moiety by an isobasic anilino group. This is attributed to the superior leaving ability from the T± intermediate of anilines, relative to isobasic pyridines, which destabilize kinetically this intermediate. The kN values for the anilinolysis of carbonates 1–3 are similar to those found in the reactions of these carbonates with secondary alicyclic amines. With the kinetic data for the anilinolysis of the title substrates and 4‐methylphenyl and 4‐chlorophenyl 2,4‐dinitrophenyl carbonates, a multiparametric equation is derived for log kN as a function of the pKa of the conjugate acids of anilines and nonleaving groups. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 191–197, 2011
Ion spectrometric detection technologies for ultra‐traces of explosives: A review
Authors: Mäkinen Marko , Nousiainen Marjaana , Sillanpää Mika
Published: February 2011

In recent years, explosive materials have been widely employed for various military applications and civilian conflicts; their use for hostile purposes has increased considerably. The detection of different kind of explosive agents has become crucially important for protection of human lives, infrastructures, and properties. Moreover, both the environmental aspects such as the risk of soil and water contamination and health risks related to the release of explosive particles need to be taken into account. For these reasons, there is a growing need to develop analyzing methods which are faster and more sensitive for detecting explosives. The detection techniques of the explosive materials should ideally serve fast real‐time analysis in high accuracy and resolution from a minimal quantity of explosive without involving complicated sample preparation. The performance of the in‐field analysis of extremely hazardous material has to be user‐friendly and safe for operators. The two closely related ion spectrometric methods used in explosive analyses include mass spectrometry (MS) and ion mobility spectrometry (IMS). The four requirements—speed, selectivity, sensitivity, and sampling—are fulfilled with both of these methods. © 2011 Wiley Periodicals, Inc., Mass Spec Rev 30:940–973, 2011
Fragmentation of toxicologically relevant drugs in positive‐ion liquid chromatography–tandem mass spectrometry
Authors: Niessen W.M.A.
Published: February 2011

The identification of drugs and related compounds by LC–MS–MS is an important analytical challenge in several application areas, including clinical and forensic toxicology, doping control analysis, and environmental analysis. Although target‐compound based analytical strategies are most frequently applied, at some point the information content of the MS–MS spectra becomes relevant. In this article, the positive‐ion MS–MS spectra of a wide variety of drugs and related substances are discussed. Starting point was an MS–MS mass spectral library of toxicologically relevant compounds, available on the internet. The positive‐ion MS–MS spectra of ∼570 compounds were interpreted by chemical and therapeutic class, thus involving a wide variety of drug compound classes, such benzodiazepines, beta‐blockers, angiotensin‐converting enzyme inhibitors, phenothiazines, dihydropyridine calcium channel blockers, diuretics, local anesthetics, vasodilators, as well as various subclasses of anti‐diabetic, antidepressant, analgesic, and antihistaminic drugs. In addition, the scientific literature was searched for available MS–MS data of these compound classes and the interpretation thereof. The results of this elaborate study are presented in this article. For each individual compound class, the emphasis is on class‐specific fragmentation, as discussing fragmentation of all individual compounds would take far too much space. The recognition of class‐specific fragmentation may be quite informative in determining the compound class of a specific unknown, which may further help in the identification. In addition, knowledge on (class‐specific) fragmentation may further help in the optimization of the selectivity in targeted analytical approaches of compounds of one particular class. © 2011 Wiley Periodicals, Inc., Mass Spec Rev 30:626–663, 2011
In vitro bioaccessibility and gut biotransformation of polyphenols present in the water‐insoluble cocoa fraction
Authors: Fogliano Vincenzo , Corollaro Maria Laura , Vitaglione Paola , Napolitano Aurora , Ferracane Rosalia , Travaglia Fabiano , Arlorio Marco , Costabile Adele , Klinder Annett , Gibson Glenn
Published: February 2011

Scope: Cocoa, especially the water‐insoluble cocoa fraction (WICF), is a rich source of polyphenols. In this study, sequential in vitro digestion of the WICF with gastrointestinal enzymes as well as its bacterial fermentation in a human colonic model system were carried out to investigate bioaccessibility and biotransformation of WICF polyphenols, respectively.

Methods and results: The yield of each enzymatic digestion step and the total antioxidant capacity (TAC) were measured and solubilized phenols were characterized by MS/MS. Fermentation of WICF and the effect on the gut microbiota, SCFA production and metabolism of polyphenols was analyzed. In vitro digestion solubilized 38.6% of WICF with pronase and Viscozyme L treatments releasing 51% of the total phenols from the insoluble material. This release of phenols does not determine a reduction in the total antioxidant capacity of the digestion‐resistant material. In the colonic model WICF significantly increased of bifidobacteria and lactobacilli as well as butyrate production. Flavanols were converted into phenolic acids by the microbiota following a concentration gradient resulting in high concentrations of 3‐hydroxyphenylpropionic acid (3‐HPP) in the last gut compartment.

Conclusion: Data showed that WICF may exert antioxidant action through the gastrointestinal tract despite its polyphenols being still bound to macromolecules and having prebiotic activity.
Retrospective estimation and correction of physiological artifacts in fMRI by direct extraction of physiological activity from MR data
Authors: Le Tuong Huu , Hu Xiaoping
Published: February 2011

A physiological artifact reduction method based on extracting respiratory motion and cardiac pulsation directly from functional MR data is described. In fast low angle shot (FLASH), respiratory cycles are derived utilizing the phase of the center of a navigator echo, in echo‐planar imaging (EPI) from the phase of the center κ‐space point. Cardiac cycles are determined from projections obtained from the navigator echo (FLASH) and the center κ‐space line (EPI). Because direct extraction of physiological parameters eliminates the need for external monitoring, the method can be more readily implemented. Experimental results illustrate that the technique provides effective compensation for physiology‐related signal fluctuations in functional MRI and performs as well as the retrospective technique using external physiological monitoring. Key words: fMRI; motion artifacts; physiological motion; image processing.
Simultaneous magnetic resonance phase and magnitude temperature maps in muscle
Authors: Cline Harvey E. , Hynynen Kullervo , Schneider Erika , Hardy Christopher J. , Maier Stefan E. , Watkins Ronald D. , Jolesz Ferenc A.
Published: February 2011

Noninvasive magnetic resonance temperature maps that are used to monitor thermal ablation of tissue are described. In magnetic resonance images, thermally induced proton nuclear magnetic resonance frequency shifts, and changes in the longitudinal relaxation time produce both phase and magnitude changes in the MR signal. Temperature maps with improved sensitivity are derived from the complex‐difference nuclear magnetic resonance signal. Bovine muscle specimens were heated with focused ultrasound to model thermal surgery and create a known thermal distribution to test the method. Resulting MR images acquired in 2 s produce temperature maps with 1 mm resolution and 2°C temperature sensitivity. The temperature sensitivity was increased by extending the acquisition to 5 s, by decreasing the receiver bandwidth, and increasing the echo time.
A forward‐subtraction procedure for removing hyperfine artifacts in electron paramagnetic resonance imaging
Authors: Kuppusamy Periannan , Zweier Jay L.
Published: February 2011

The potential for using electron paramagnetic resonance (EPR) imaging in biological applications has been limited by the lack of ideal single‐line imaging probes. The commonly used nitroxides exhibit multiple lines, causing either hyper‐fine‐based limitations in the maximum obtainable image resolution or hyperfine‐based artifacts in the reconstructed image. The application of a numerical method, based on forward‐subtraction principles for removing hyperfine artifacts in the measured projections is reported. It is demonstrated by using computer simulations, imaging of phantoms, and imaging of rat hearts, that marked enhancement in image quality and resolution can be obtained by removing the hyper‐fine‐imposed limit on the gradient magnitude and performing postacquisition corrections for removing hyperfine artifacts in the image.
Three‐Dimensional gated EPR imaging of the beating heart: Time‐resolved measurements of free radical distribution during the cardiac contractile cycle
Authors: Kuppusamy Periannan , Chzhan Michael , Wang Penghai , Zweier Jay L.
Published: February 2011

In vivo or ex vivo EPR imaging, EPRI, has been established as a powerful technique for determining the spatial distribution of free radicals and other paramagnetic species in living organs and tissues. While instrumentation capable of performing EPR imaging of free radicals in whole tissues and isolated organs has been previously reported, it was not possible to image rapidly moving organs such as the beating heart Therefore instrumentation was developed to enable the performance of gated‐spectroscopy and imaging on isolated beating rat hearts at L‐band. A synchronized pulsing and timing system capable of gated acquisitions of up to 256 images per cycle, with rates of up to 16 Hz was developed. The temporal and spatial accuracy of this instrumentation was verified using a specially designed beating heart‐shaped isovolumic phantom with electromechanically driven sinusoidal motion at a cycle rate of 5 Hz. Gated EPR imaging was performed on a series of isolated rat hearts perfused with nitroxide spin labels. These hearts were paced at a rate of 6 Hz with either 16 or 32 gated images acquired per cardiac contractile cycle. The images enabled visualization of the time‐dependent alterations in the free radical distribution and anatomical structure of the heart that occur during the cardiac cycle.