bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor necrosis factor α release in peripheral blood mononuclear cells of cutaneous lupus and dermatomyositis patients
Authors: Nabatian Adam S , Bashir Muhammad M , Wysocka Maria , Sharma Meena , Werth Victoria P 
Published: January 2012

Abstract
Introduction
Several studies have reported that TNFα is substantially increased within skin lesions of patients with discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE) and dermatomyositis (DM) compared to controls. Elevated TNFα has been reported in the sera of some patients with systemic lupus erythematosus, DLE and SCLE, but not in the sera of patients with DM. Because of the key pathogenic role of autoimmunity in these diseases, in this study we sought to evaluate TNFα production by a readily available source of immune cells (namely, peripheral blood mononuclear cells (PBMCs)) taken from controls and from patients with cutaneous lupus or DM.

Methods
Freshly isolated PBMCs were cultured overnight, and TNFα protein accumulation in conditioned medium was determined. In addition, flow cytometry using cell-type-specific markers was performed to determine the sources of TNFα. One-way analysis of variance and Dunnett's multiple comparisons test were performed for statistical comparisons.

Results
Accumulation of TNFα protein in conditioned medium containing PBMCs from DLE patients, but not from SCLE, TLE or DM patients, was significantly greater (19-fold) than that from controls (P < 0.001). In DLE PBMCs, increased TNFα was produced by circulating monocytes and myeloid dendritic cells (mDCs). The mean TNFα fluorescence intensity, but not the total number, of both monocytes and mDCs (P < 0.01) from DLE patients was significantly greater (2.3-fold) than that of controls. There were significantly more (13.3-fold) mDCs with intracellular TNFα in blood from DLE patients (P < 0.001) and DM patients (P < 0.001) compared to controls. Most importantly, a positive correlation was seen in DLE patients between their disease activity measured using the Cutaneous Lupus Erythematosus Disease Area and Severity Index and TNFα protein secretion (r = 0.61, P < 0.08).

Conclusions
TNFα protein production by PBMCs is greater in DLE patients than in patients with other cutaneous forms of lupus and DM or in controls. Flow cytometric studies demonstrated that circulating monocytes and mDCs contributed to this increased TNFα production. Monocytes and mDCs are present in lesional skin, and the increased TNFα production by these cells and other PBMCs likely increase the number of inflammatory cells seen in DLE skin relative to other subsets of cutaneous lupus erythematosus and DM. These results provide a possible biological explanation for the denser infiltrate seen in DLE relative to DM.
First sedimentary record of the pre-obduction convergence in New Caledonia: formation of an Early Eocene accretionary complex in the north of Grande Terre and emplacement of the ‘Montagnes Blanches’ nappe
Authors: Maurizot Pierre 
Published: January 2012

Abstract
New Caledonia lies at the northern tip of the Norfolk ridge, a continental fragment separated from the east Gondwana margin during the Late Cretaceous. Stratigraphic data for constraining the convergence that led to ophiolitic nappes being obducted over Grande Terre during the Eocene are both few and inaccurate. To try and fill this gap and determine the onset of the convergence, we investigated the lithology, sedimentology, biostratigraphy and geodynamic context of the Late Cretaceous – Palaeogene sedimentary cover-rock succession of northern New Caledonia. We were able to establish new stratigraphic correlations between the sedimentary units, which display large southwest-verging overfolds detached along a basal argillite series, and reinterpret their interrelationships. The sediments from the Cretaceous-Paleocene interval were deposited in a post-rift pelagic environment and are mainly biogenic with minimal terrigenous input. From the base up, they comprise black organic-rich sulphide-bearing argillite, black chert (silicified equivalent of the argillite), micritic with chert, and micrite rich in planktonic foraminifera. These passive-margin deposits are found regionally on the Norfolk Ridge down to New Zealand, and on the Lord Howe Rise, and were controlled primarily by regional or global environmental factors. The overlying Eocene deposits mark a change to an active-margin regime with distal calciturbidite and proximal breccia representing the earliest Paleogene flysch-type deposits in New Caledonia. The change from an extensional to a compressive regime marks the beginning of the pre-obduction convergence and can be assigned fairly accurately in the Koumac–Gomen area to the end of the Early Eocene (Late Ypresian, Biozone E7) at c 50 Ma. From this period on, the post-Late Cretaceous cover in northern New Caledonia was caught up and recycled in a southwest-verging accretionary complex ahead of which flysch was deposited in a flexural foreland basin. The system prograded southwards until the Late Eocene collisional stage, when the continental Norfolk ridge entered the convergence zone and blocked it. At this point the autochthonous and parautochthonous sedimentary cover and overlying flysch of northern New Caledonia was thrust over the younger flysch to the south to form a newly defined allochthonous unit, the ‘Montagnes Blanches’ nappe, that is systematically intercalated between the flysch and the obducted ophiolite units throughout Grande Terre.
Topologies on central extensions of von Neumann algebras
Authors: Ayupov Shavkat , Kudaybergenov Karimbergen , Djumamuratov Rauaj 
Published: January 2012

Abstract
Given a von Neumann algebra M, we consider the central extension E(M) of M. We introduce the topology t
c(M) on E(M) generated by a center-valued norm and prove that it coincides with the topology of local convergence in measure on E(M) if and only if M does not have direct summands of type II. We also show that t
c(M) restricted to the set E(M)h of self-adjoint elements of E(M) coincides with the order topology on E(M)h if and only if M is a σ-finite type Ifin von Neumann algebra.
On a space of smooth functions on a convex unbounded set in ℝn admitting holomorphic extension in ℂn
Authors: Musin Il’dar , Yakovleva Polina 
Published: January 2012

Abstract
For some given logarithmically convex sequence M of positive numbers we construct a subspace of the space of rapidly decreasing infinitely differentiable functions on an unbounded closed convex set in ℝn. Due to the conditions on M each function of this space admits a holomorphic extension in ℂn. In the current article, the space of holomorphic extensions is considered and Paley-Wiener type theorems are established. To prove these theorems, some auxiliary results on extensions of holomorphic functions satisfying some weighted L
2-bounds in a domain of holomorphy in ℂn are obtained with the aid of L. Hörmander’s method of L
2-bounds for the
$$\bar \partial$$
operator. Also, some new facts on the Fourier-Laplace transform of tempered distributions complementing some well-known results of V.S. Vladimirov are employed.
Leitstruktur‐orientierte Synthese: eine Alternative für die Synthesechemie
Authors: Nadin Alan , Hattotuwagama Channa , Churcher Ian 
Published: January 2012

AbstractZur Herstellung von niedermolekularen Verbindungen für Wirkstoff‐Forschungsprogramme bleibt die pharmazeutische Industrie ausschließlich auf Methoden der Synthesechemie angewiesen. Die Bedeutung der physikochemischen Eigenschaften dieser Verbindungen für die Ermittlung ihres Erfolgs in der Wirkstoffentwicklung ist inzwischen gut bekannt, aber die hier vorgestellten Daten lassen darauf schließen, dass viele Synthesemethoden ungewollt prädisponiert sind, Verbindungen mit schlechteren wirkstoffähnlichen Eigenschaften zu bilden. Diese Tendenz kann Auswirkungen auf die ersten Phasen der Treffer‐ und Leitstruktursuche in der Wirkstoff‐Forschung haben, wenn eine größere Zahl von Verbindungen durch Array‐Verfahren hergestellt wird. Wir beschreiben hier erstmals das Konzept der Leitstruktur‐orientierten Synthese und die Möglichkeit, durch ihre Anwendung das Spektrum und die Qualität von Verbindungen für die Entwicklung neuer Medikamente zu erhöhen.
Rilonacept (Interleukin‐1 Trap) in the prevention of acute gout flares during initiation of urate‐lowering therapy: Results of a phase II randomized, double‐blind, placebo‐controlled trial
Authors: Schumacher H. Ralph , Sundy John S. , Terkeltaub Robert , Knapp Howard R. , Mellis Scott J. , Stahl Neil , Yancopoulos George D. , Soo Yuhwen , King‐Davis Shirletta , Weinstein Steven P. , Radin Allen R. ,   0619 Study Group
Published: January 2012

AbstractObjectiveTo evaluate the interleukin‐1 inhibitor rilonacept (Interleukin‐1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate‐lowering therapy.MethodsIn this double‐blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained.ResultsBaseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept‐ and placebo‐treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept‐treated patients (98%) compared with placebo‐treated patients (79%) completed the primary 12‐week evaluation period (P = 0.015).ConclusionThe current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate‐lowering therapy, with a favorable safety profile.
Activation of target signal transducers utilizing chimeric receptors with signaling‐molecule binding motifs
Authors: Saka Koichiro , Kawahara Masahiro , Ueda Hiroshi , Nagamune Teruyuki 
Published: January 2012

AbstractCellular fates such as proliferation, differentiation, and death are controlled by a variety of cytokine receptors, which are crucial in initiating downstream signaling cascades. To initiate signaling, the cytokine receptor cytoplasmic domain recruits specific signaling molecules with a range of tyrosine‐containing motifs. Thus, we postulate that it is possible to regulate signal transduction artificially by locating the tyrosine motif of interest into the intracellular domain of specific receptors. Construction of such artificial receptors was based on an anti‐fluorescein ScFv/c‐Mpl chimera (S‐Mpl). We selected several known tyrosine motifs from native cytokine receptors that strongly bind to their target molecule, and located them downstream of the Janus kinase (JAK) binding domain of S‐Mpl, which would be necessary for phosphorylation of the receptor. Next, we used retroviral transduction to express chimeric receptors in a murine IL‐3‐dependent pro‐B cell line, Ba/F3, which was stimulated with BSA‐fluorescein. The results indicated that each chimeric receptor preferentially activated the corresponding signaling molecule. We also examined whether the position of the tyrosine motif in the receptor could influence the activation levels of the signal transducer, and found that the chimeric receptors could activate the corresponding signaling molecule even when the tyrosine motif was distant from the JAK binding domain. Biotechnol. Bioeng. 2012; 109:1528–1537. © 2012 Wiley Periodicals, Inc.
Metabolic engineering of thermophilic Bacillus licheniformis for chiral pure D‐2,3‐butanediol production
Authors: Wang Qingzhao , Chen Tao , Zhao Xueming , Chamu Jauhleene 
Published: January 2012

Abstract2,3‐Butanediol is an important compound that can be used in many areas, especially as a platform chemical and liquid fuel. But traditional 2,3‐butanediol producing microorganisms, such as Klebsiella pneumonia and K. xoytoca, are pathogens and they can only ferment sugars at 37°C. Here, we reported a newly developed Bacillus licheniformis. A protoplast transformation system was developed and optimized for this organism. With this transformation method, a marker‐less gene deletion protocol was successfully used to knock out the ldh gene of B. licheniformis BL1 and BL3. BL1 was isolated earlier from soil for lactate production and it was further evolved to BL3 for xylose utilization. Combined with pH and aeration control, ldh mutant BL5 and BL8 can efficiently ferment glucose and xylose to D‐(−) 2,3‐butanediol at 50°C, pH 5.0. For glucose and xylose, the specific 2,3‐butanediol productivities are 29.4 and 26.1 mM/h, respectively. The yield is 0.73 mol/mol for BL8 in xylose and 0.9 mol/mol for BL5 and BL8 in glucose. The D‐(−) 2,3‐butanediol optical purity is more than 98%. As far as we know, this is the first reported high temperature butanediol producer to match the simultaneous saccharification and fermentation conditions. Therefore, it has potential to further lower butanediol producing cost with low cost lignocellulosic biomass in the near future. Biotechnol. Bioeng. 2012; 109:1610–1621. © 2012 Wiley Periodicals, Inc.
LC‐ESI‐MS/MS method for quantification of ambrisentan in plasma and application to rat pharmacokinetic study
Authors: Nirogi Ramakrishna , Kandikere Vishwottam , Komarneni Prashanth , Aleti Raghupathi , Padala NagaSuryaPrakash , Kalaikadhiban Ilayaraja 
Published: January 2012

ABSTRACTA sensitive high‐performance liquid chromatography–positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of ambrisentan in plasma. The analyte and the internal standard (armodafinil) were extracted from plasma by acetonitrile precipitation and they were separated on a reversed‐phase C18 column with a gradient program. The MS acquisition was performed with multiple reaction monitoring mode using the respective [M + H]+ ions, m/z 379–347 for ambrisentan and m/z 274–167 for the IS. The assay exhibited a linear dynamic range of 1–2000 ng/mL for ambrisentan in plasma. Acceptable precision (<10%) and accuracy (100 ± 8%) were obtained for concentrations over the standard curve range. The method was successfully applied to quantify ambrisentan concentrations in a rodent pharmacokinetic study after a single oral administration of ambrisentan at 2.5 mg/kg to rats. Following oral administration the maximum mean concentration in plasma (Cmax; 1197 ± 179 ng/mL) was achieved at 1.0 ± 0.9 h (Tmax), and the area under the curve (AUC) was 6013 ± 997 ng h/mL. Therefore, development of such a simple and sensitive method in rat plasma should translate into a method for ambrisentan in human plasma for clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.
A novel LC‐MS/MS method for simultaneous quantification of tenofovir and lamivudine in human plasma and its application to a pharmacokinetic study
Authors: Matta Murali Krishna , Burugula Laxminarayana , Pilli Nageswara Rao , Inamadugu Jaswanth Kumar , JVLN Seshagiri Rao 
Published: January 2012

ABSTRACTA new, rapid, sensitive and specific LC‐MS/MS method has been developed and validated for the simultaneous quantification of tenofovir and lamivudine in human plasma using abacavir as an internal standard. An API‐4000 LC‐MS/MS with electrospray ionization was operated in multiple‐reaction monitoring mode for the analysis. The analytes were extracted from plasma by solid‐phase extraction technique using an Oasis HLB cartridge. The reconstituted samples were chromatographed on a Chromolith ROD speed C18 column using a mixture of 0.1% formic acid in water and acetonitrile (90:10 v/v) at a flow‐rate of 1 mL/min. The method was validated as per the FDA guidelines. The calibration curves were found to be linear in the range of 5–600 ng/mL for tenofovir and 25– 4000 ng/mL for lamivudine. The intra‐ and inter‐day precision and accuracy results were well within the acceptable limits. A run time of 2.8 min consumed for each sample made it possible to analyze more samples per day. The proposed assay method was found to be applicable to a pharmacokinetic study in human male volunteers. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis and Photophysical Properties of Fullerene–Phthalocyanine–Porphyrin Triads and Pentads
Authors: Enes Roger F. , Cid Juan‐José , Hausmann Anita , Trukhina Olga , Gouloumis Andreas , Vázquez Purificación , Cavaleiro José A. S. , Tomé Augusto C. , Guldi Dirk M. , Torres Tomás 
Published: January 2012

AbstractThe synthesis and photophysical properties of several fullerene–phthalocyanine–porphyrin triads (1–3) and pentads (4–6) are described. The three photoactive moieties were covalently connected in an one‐step synthesis through 1,3‐dipolar cycloaddition to C60 of the corresponding azomethine ylides generated in situ by condensation reaction of a substituted N‐porphyrinylmethylglycine derivative and an appropriated formyl phthalocyanine or a diformyl phthalocyanine derivative, respectively. ZnP‐C60‐ZnPc (3), (ZnP)2‐ZnPc‐(C60)2 (6), and (H2P)2‐ZnPc‐(C60)2 (5) give rise upon excitation of their ZnP or H2P components to a sequence of energy and charge‐transfer reactions with, however, fundamentally different outcomes. With (ZnP)2‐ZnPc‐(C60)2 (6) the major pathway is an highly exothermic charge transfer to afford (ZnP)(ZnP.+)‐ZnPc‐(C60.−)(C60). The lower singlet excited state energy of H2P (i.e., ca. 0.2 eV) and likewise its more anodic oxidation (i.e., ca. 0.2 V) renders the direct charge transfer in (H2P)2‐ZnPc‐(C60)2 (5) not competitive. Instead, a transduction of singlet excited state energy prevails to form the ZnPc singlet excited state. This triggers then an intramolecular charge transfer reaction to form exclusively (H2P)2‐ZnPc.+‐(C60.−)(C60). A similar sequence is found for ZnP‐C60‐ZnPc (3).
Anodic Oxidation as Green Alternative for Removing Diethyl Phthalate from Wastewater Using Pb/PbO2and Ti/SnO2Anodes
Authors: Vazquez‐Gomez Lourdes , de Battisti Achille , Ferro Sergio , Cerro Monica , Reyna Silvia , Martínez‐Huitle Carlos A. , Quiroz Marco A. 
Published: January 2012

AbstractThe electrochemical oxidation (EO) of diethyl phthalate (DEP) in aqueous solution was studied at Pb/PbO2and Ti/SnO2anode materials under galvanostatic‐experimental conditions. Results obtained clearly demonstrated that the anode plays a significant role for the optimization of the oxidation process, deciding the mechanisms and by‐products formed. DEP and by‐products of oxidation were also analyzed during various stages of the electrolysis reaction by HPLC and GC/MS techniques. Before the analysis by GC/MS technique, the samples were treated by solid phase microextraction (SPME) in order to concentrate the compounds from the reaction solution and identify all electrolysis intermediates. Current efficiencies (instantaneous current efficiency; ICE and total current efficiency; TCE) achieved during EO experiments were dependent on anode used and current density (20–40 mA cm−2) at 40°C. The results obtained demonstrated that the environmental electrochemical methods can be a feasible alternative for the wastewater treatment containing hazardous phthalates.
Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle‐invasive transitional cell carcinoma of the bladder
Authors: Blick Christopher , Hall Peter , Pwint Thinn , Al‐Terkait Faisal , Crew Jeremy , Powles Thomas , Macaulay Valentine , Munro Nicholas , Douglas David , Kilbey Neviana , Protheroe Andrew , Chester John D. 
Published: January 2012

AbstractBACKGROUND:Meta‐analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin‐based combination regimens in the radical treatment of muscle‐invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose‐intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway.METHODS:Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro‐oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m2, vinblastine 3 mg/m2, doxorubicin 30 mg/m2, and cisplatin 70 mg/m2) were given at 2‐week intervals, with granulocyte colony‐stimulating factor support, prior to either radical surgery or radical radiotherapy.RESULTS:All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two‐year disease‐free and overall survival were 65% and 77%, respectively.CONCLUSIONS:AMVAC is safe and appears to be a well‐tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials. Cancer 2012. © 2012 American Cancer Society.
Site‐specific transgenesis in Xenopus
Authors: Zuber Michael E. , Nihart Heather S. , Zhuo Xinming , Babu Sudha , Knox Barry E. 
Published: January 2012

AbstractTransgenesis is an essential, powerful tool for investigating gene function and the activities of enhancers, promoters, and transcription factors in the chromatin environment. In Xenopus, current methods generate germ‐line transgenics by random insertion, often resulting in mosaicism, position‐dependent variations in expression, and lab‐to‐lab differences in efficiency. We have developed and tested a Xenopus FLP‐FRT recombinase‐mediated transgenesis (X‐FRMT) method. We demonstrate transgenesis of Xenopus laevis by FLP‐catalyzed recombination of donor plasmid cassettes into F1 tadpoles with host cassette transgenes. X‐FRMT provides a new method for generating transgenic Xenopus. Once Xenopus lines harboring single host cassettes are generated, X‐FRMT should allow for the targeting of transgenes to well‐characterized integration site(s), requiring no more special reagents or training than that already common to most Xenopus labs. genesis 50:325–332, 2012. © 2012 Wiley Periodicals, Inc.