bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 trial of pemetrexed in children and adolescents with refractory solid tumors: A Children's Oncology Group study
Authors: Warwick Anne B. , Malempati Suman , Krailo Mark , Melemed Allen , Gorlick Richard , Ames Matthew M. , Safgren Stephanie L. , Adamson Peter C. , Blaney Susan M. 
Published: June 2012

AbstractBackgroundPemetrexed is a multi‐targeted antifolate that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors, including CNS tumors, to estimate the response rate and further define its toxicity profile.ProcedurePemetrexed, at a dose of 1910 mg/m2, was administered as a 10‐minute intravenous infusion every 21 days. Patients also received vitamin B12, daily multivitamin supplementation, and dexamethasone. A two‐stage design (10 + 10) was employed in each of the following disease strata: osteosarcoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, and non‐brainstem high‐grade glioma.ResultsSeventy‐two eligible subjects (39 males) were enrolled. Median age was 11 years (range 3–23). Sixty‐eight were evaluable for response. The median number of cycles administered was 2 (range 1–13). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4–13) cycles, was observed in five patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n = 1 each). Neutropenia (44%), anemia (35%), and elevated alanine transaminase (35%) attributable to pemetrexed were the most commonly recurring toxicities observed in patients receiving multiple cycles. Other toxicities attributed to pemetrexed occurring in ≥10% of cycles included thrombocytopenia (30%), fatigue (18%), nausea (14), hyperglycemia (13%), rash (11%), vomiting (13%), and hypophosphatemia (11%).ConclusionsPemetrexed, administered as an intravenous infusion every 21 days, was tolerable in children and adolescents with refractory solid tumors, including CNS tumors, but did not show evidence of objective anti‐tumor activity in the childhood tumors studied. Pediatr Blood Cancer 2013;60:237–241. © 2012 Wiley Periodicals, Inc.
Metronomic therapy for malignant peripheral nerve sheath tumor in neurofibromatosis type 1
Authors: Chaudhary Narendra , Borker Anupama 
Published: June 2012

AbstractMalignant peripheral nerve sheath tumor (MPNST) is a highly aggressive tumor especially in the patients with neurofibromatosis type 1 (NF1). Without a complete surgical excision, prognosis is guarded. We describe a 10‐year‐old male with NF1 with MPNST, who had a local relapse within 5 weeks of surgical excision. Chemoradiotherapy did not result in tumor regression. Initiation of palliative oral metronomic therapy resulted in complete remission after six cycles. The patient continues to be in remission, 20 months after completion of nine cycles of metronomic therapy. Metronomic therapy may be effective in MPNST where conventional chemotherapy and radiotherapy fails. Pediatr Blood Cancer 2012; 59: 1317–1319. © 2012 Wiley Periodicals, Inc.
RAFT polymerization of vinyl methacrylate and subsequent conjugation via enzymatic thiol‐ene chemistry
Authors: Yhaya Firdaus , Sutinah Arlingga , Gregory Andrew M. , Liang Mingtao , Stenzel Martina H. 
Published: June 2012

AbstractThe polymerization of vinyl methacrylate (VMA) allows the synthesis of polymers with pendant double bonds. When this polymerization was undertaken in the presence of 2‐cyanopropyl dithiobenzoate as reversible addition–fragmentation chain transfer agent, it led almost exclusively to vinylester functional sidegroups, which were available for further reactions. The vinylester functionality could not be functionalized using common thiol‐ene catalysts, but could be activated using Candida antarctica lipase B (CAL‐B) (Novozyme 435). The reaction between PVMA and various thiols in N, N‐dimethyl formamide in the presence of CAL‐B led exclusively to the formation of the anti‐Markovnikov product. The rate of reaction between PVMA and 1‐butanethiol was monitored using 1H NMR. The reaction was complete within 72 h. Similar results were obtained with other small‐sized thiols such as 2‐mercaptoethanol, 3‐mercaptopropionic acid, and 2‐(trimethylsilyl)ethanethiol, while more bulky thiols, such as secondary thiols, thiols with long alkyl chains, and sterically demanding thiols, such as mono(6‐deoxy‐6‐mercapto)‐β‐cyclodextrin, only led to lower conversions. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Producing bimodal molecular weight distribution polymers through facile one‐pot/one‐step RAFT polymerization
Authors: Jiang Hongjuan , Zhang Lifen , Qin Jian , Zhang Wei , Cheng Zhenping , Zhu Xiulin 
Published: June 2012

AbstractWell‐defined bimodal molecular weight distribution (MWD) polystyrene and polystyrene‐b‐poly(acrylonitrile) were successfully synthesized using a pair of mono/difunctional trithiocarbonate RAFT agents 1 and 2 via one‐pot RAFT polymerization. The kinetics of RAFT polymerization for styrene in bulk with a molar ratio of [St]0:[AIBN]0:[1]0:[2]0 = 1200:1:2.5:2.5 was studied at 75°C. The results indicated that the system showed excellent controllability and “living” characteristics to both higher and lower molecular weight fractions, providing an efficient and facile way to producing bimodal MWD (co)polymers with both controlled molecular weight (MW) and MWD in molecular level, and the plausible mechanism was discussed in this work. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Longitudinal analysis of the relations between opportunities to learn about science and the development of interests related to science
Authors: Alexander Joyce M. , Johnson Kathy E. , Kelley Ken 
Published: June 2012

AbstractRelations between parental reports of children's interests related to science and opportunities for science learning were examined longitudinally in 192 children between ages 4 and 7 years. Science interests were tracked during 1‐year periods (ages 4–5, 5–6, and 6–7) and were more prevalent among boys, particularly prior to age 6 years. Gender differences did emerge in terms of frequencies of opportunities for science learning during all 3 years. Longitudinal path analyses tested relations between children's science interests and their opportunities for science learning. Our data suggest that early science interests were strong predictors of later opportunities to engage in informal science learning, whereas the opposite pattern (early opportunities predicting later science interests) was not found. Young girls' expressed science interests led parents to subsequently increase opportunities for science learning during the following year. Although boys followed this pattern early in the study, over time boys received similar levels of science opportunities regardless of their interest. Bases for gender differences in early science interests and implications for later science learning in school are considered. © 2012 Wiley Periodicals, Inc. Sci Ed 96:763–786, 2012
Probabilistic verification of Herman’s self-stabilisation algorithm
Authors: Kwiatkowska Marta , Norman Gethin , Parker David 
Published: June 2012

Abstract

Herman’s self-stabilisation algorithm provides a simple randomised solution to the problem of recovering from faults in an
N
-process token ring. However, a precise analysis of the algorithm’s maximum execution time proves to be surprisingly difficult. McIver and Morgan have conjectured that the worst-case behaviour results from a ring configuration of three evenly spaced tokens, giving an expected time of approximately 0.15
N
2
. However, the tightest upper bound proved to date is 0.64
N
2
. We apply probabilistic verification techniques, using the probabilistic model checker PRISM, to analyse the conjecture, showing it to be correct for all sizes of the ring that can be exhaustively analysed. We furthermore demonstrate that the worst-case execution time of the algorithm can be reduced by using a biased coin.
On termination and invariance for faulty channel machines
Authors: Bouyer Patricia , Markey Nicolas , Ouaknine Joël , Schnoebelen Philippe , Worrell James 
Published: June 2012

Abstract

A
channel machine
consists of a finite controller together with several fifo channels; the controller can read messages from the head of a channel and write messages to the tail of a channel. In this paper we focus on channel machines with
insertion errors
, i.e., machines in whose channels messages can spontaneously appear. We consider the
invariance
problem: does a given insertion channel machine have an infinite computation all of whose configurations satisfy a given predicate? We show that this problem is primitive-recursive if the predicate is closed under message losses. We also give a non-elementary lower bound for the invariance problem under this restriction. Finally, using the previous result, we show that the satisfiability problem for the safety fragment of Metric Temporal Logic is non-elementary.
Deterministic concurrent strategies
Authors: Winskel Glynn 
Published: June 2012

Abstract

Nondeterministic concurrent strategies—those strategies compatible with copy-cat behaving as identity w.r.t. composition—have been characterised as certain maps of event structures. This leads to a bicategory of general concurrent games in which the maps are nondeterministic concurrent strategies. This paper explores the important sub-bicategory of
deterministic
concurrent strategies. It is shown that
deterministic
strategies in a game can be identified with certain subgames, with the benefit that the bicategory of deterministic games becomes equivalent to a technically-simpler order-enriched category. Via a characterisation, deterministic strategies are shown to coincide with the
receptive ingenuous strategies
of Melliès and Mimram. Deterministic strategies determine
closure operators
, in accord with an early definition of Abramsky and Melliès. Known subcategories appear as special cases: Berry’s order-enriched category of
dI-domains and stable functions
arises as a full subcategory in which the games comprise solely of Player moves; the
`simple games’
of Hyland et al., a basis for much of game semantics, form a subcategory in which the games permit no concurrency, Player-Opponent moves alternate and Opponent always moves first.
The Safety-Critical Java memory model formalised
Authors: Cavalcanti Ana , Wellings Andy , Woodcock Jim 
Published: June 2012

Abstract
Safety-Critical Java (SCJ) is a version of Java for real-time programming, restricted to facilitate certification of implementations of safety-critical systems. Its development is the result of an international effort involving experts from industry and academia. What we provide here is, as far as we know, the first formalisation of the SCJ model of memory regions. We use Hoare and He’s unifying theories of programming (UTP), enabling the integration of our theory with refinement models for object orientation and concurrency. In developing the SCJ theory, we also make a contribution to UTP by providing a general theory of invariants (an instance of which is used in the SCJ theory). The results presented here are a first essential ingredient to formalise the novel programming paradigm embedded in SCJ, and enable the justification and development of formal reasoning techniques based on refinement.
Safety and biomarker effects of solanezumab in patients with Alzheimer's disease
Authors: Farlow Martin , Arnold Steven E. , van Dyck Christopher H. , Aisen Paul S. , Snider B. Joy , Porsteinsson Anton P. , Friedrich Stuart , Dean Robert A. , Gonzales Celedon , Sethuraman Gopalan , DeMattos Ronald B. , Mohs Richard , Paul Steven M. , Siemers Eric R. 
Published: June 2012

AbstractObjectivesTo assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of 12 weekly infusions of solanezumab, an anti‐β‐amyloid (Aβ) antibody, in patients with mild‐to‐moderate Alzheimer's disease. Cognitive measures were also obtained.MethodsIn this phase 2, randomized, double‐blind, placebo‐controlled clinical trial, 52 patients with Alzheimer's disease received placebo or antibody (100 mg every 4 weeks, 100 mg weekly, 400 mg every 4 weeks, or 400 mg weekly) for 12 weeks. Safety and biomarker evaluations continued until 1 year after randomization. Both magnetic resonance imaging and cerebrospinal fluid (CSF) examinations were conducted at baseline and after the active treatment period. The Aβ concentrations were measured in plasma and CSF, and the Alzheimer's Disease Assessment Scale–cognitive portion was administered.ResultsClinical laboratory values, CSF cell counts, and magnetic resonance imaging scans were unchanged by treatment, and no adverse events could be clearly related to antibody administration. Total (bound to antibody and unbound) Aβ1–40 and Aβ1–42 in plasma increased in a dose‐dependent manner. Antibody treatment similarly increased total Aβ1–40 and Aβ1–42 in CSF. For patients taking 400 mg weekly, antibody treatment decreased unbound Aβ1–40 in CSF (P < .01), but increased unbound Aβ1–42 in CSF in a dose‐dependent manner. The Alzheimer's Disease Assessment Scale–cognitive portion was unchanged after the 12‐week antibody administration.ConclusionsAntibody administration was well tolerated with doses up to 400 mg weekly. The dose‐dependent increase in unbound CSF Aβ1–42 suggests that this antibody may shift Aβ equilibria sufficiently to mobilize Aβ1–42 from amyloid plaques.
Inclusion of radiobiological factors in prostate brachytherapy treatment planning
Authors: Knaup Courtney , Mavroidis Panayiotis , Swanson Gregory , Stathakis Sotirios , Baltas Dimos , Papanikolaou Niko 
Published: June 2012

AbstractPurpose: Comparison of prostate seed implant treatment plans is currently based on evaluation of dose-volume histograms and doses to the tumour and normal structures. However, these do not account for effects of varying dose-rate, tumour repopulation and other biological effects. In this work, incorporation of the radiobiological response is used to obtain a more inclusive and clinically relevant treatment plan evaluation tool.Materials and Methods: Ten patients were evaluated. For each patient, six different treatment plans were created on the Prowess system. Plans with iodine-125 used a prescription dose of 145 Gy while plans with palladium-103 used 115 Gy. The biologically effective dose was used together with the tumour control probability and the normal tissue complication probabilities of urethra, bladder, rectum and surrounding tissue to evaluate the effectiveness of each treatment plan. Results from the radiobiological evaluation were compared to standard dose quantifiers.Results: The use of response probabilities is seen to provide a simpler means of treatment evaluation compared to standard dose quantifiers. This allows for different treatment plans to be quickly compared. Additionally, the use of radiobiologically-based plan evaluation allows for optimisation of seed type and initial seed strengths to find the ideal balance of TCP and NTCP.Conclusion: The goal of this work was to incorporate the biological response to obtain a more complete and clinically relevant treatment plan evaluation tool. This resulted in a simpler means of plan evaluation that may be used to compare and optimise prostate seed implant treatment plans.
Particle fluxes and condensational uptake over sea ice during COBRA
Authors: Whitehead J. D. , Dorsey J. R. , Gallagher M. W. , Flynn M. J. , McFiggans G. , Carpenter L. J. 
Published: June 2012

Particle fluxes were measured over sea ice at Hudson Bay, Canada, during the COBRA experiment in February and March, 2008. Eddy covariance particle fluxes were measured using a condensation particle counter and an ultrasonic anemometer on a 2.5 m mast on the sea ice. After applying appropriate corrections and filtering, the mean net deposition velocity was 0.12 ± 0.11 mm s−1 for particles measured with a CPC 3776 (lower size threshold, Dp50 = 2.5 nm) and was at the detection limit of the measurement system. No evidence of nucleation events was seen. Two optical particle counters (at heights 0.2 and 1.35 m on the mast) allowed size segregated fluxes of particles in the accumulation and coarse mode diameter range 0.3–20 μm to be derived using the aerodynamic flux gradient method. Strong net emission fluxes were observed around midday, 3rd March, when winds increased to around 10 m s−1, suggesting ice particle resuspension. The fluxes during this period had a significant influence on the derived condensational loss rate to the available particle surfaces, kt. Number fluxes were greatest in the smallest size channels, while the largest sizes dominated the mass flux. Number fluxes also increased with wind speed, and this relationship was strongest for the smaller sizes. Particle mass size distributions showed an enhanced mode around 400 nm (dry size). Values of kt were well approximated by the molecular regime and were found to be much smaller and less variable than values derived for marine air.
Metabolic stratification driven by surface and subsurface interactions in a terrestrial mud volcano
Authors: Cheng Ting-Wen , Chang Yung-Hsin , Tang Sen-Lin , Tseng Ching-Hung , Chiang Pei-Wen , Chang Kai-Ti , Sun Chih-Hsien , Chen Yue-Gau , Kuo Hung-Chi , Wang Chun-Ho , Chu Pao-Hsuan , Song Sheng-Rong , Wang Pei-Ling , Lin Li-Hung 
Published: June 2012

Abstract
Terrestrial mud volcanism represents the prominent surface geological feature, where fluids and hydrocarbons are discharged along deeply rooted structures in tectonically active regimes. Terrestrial mud volcanoes (MVs) directly emit the major gas phase, methane, into the atmosphere, making them important sources of greenhouse gases over geological time. Quantification of methane emission would require detailed insights into the capacity and efficiency of microbial metabolisms either consuming or producing methane in the subsurface, and establishment of the linkage between these methane-related metabolisms and other microbial or abiotic processes. Here we conducted geochemical, microbiological and genetic analyses of sediments, gases, and pore and surface fluids to characterize fluid processes, community assemblages, functions and activities in a methane-emitting MV of southwestern Taiwan. Multiple lines of evidence suggest that aerobic/anaerobic methane oxidation, sulfate reduction and methanogenesis are active and compartmentalized into discrete, stratified niches, resembling those in marine settings. Surface evaporation and oxidation of sulfide minerals are required to account for the enhanced levels of sulfate that fuels subsurface sulfate reduction and anaerobic methanotrophy. Methane flux generated by in situ methanogenesis appears to alter the isotopic compositions and abundances of thermogenic methane migrating from deep sources, and to exceed the capacity of microbial consumption. This metabolic stratification is sustained by chemical disequilibria induced by the mixing between upward, anoxic, methane-rich fluids and downward, oxic, sulfate-rich fluids.
Inhibitors of Cytosolic Phospholipase A2α as Anti-inflammatory Drugs
Authors: LEHR MATTHIAS 
Published: June 2012

Arachidonic acid derivatives, like prostaglandins and leukotrienes, as well as the alkyl-ether phospholipid platelet-activating factor (PAF) are highly active substances with diverse biological actions. Elevated levels of these lipid mediators in response to a variety of stimuli have been implicated in the pathology of many inflammatory diseases. The rate-limiting step in the generation of prostaglandins, leukotrienes and PAF, respectively, is the cleavage of the sn-2-ester of membrane phospholipids by a phospholipase A2 (PLA2). Among the superfamily of PLA2 enzymes, cytosolic PLA2α (cPLA2α, also referred to as group IVA PLA2) is thought to play the primary role in this biochemical reaction. Therefore, inhibition of cPLA2α activity is an attractive approach to the control of inflammatory disorders.
In this chapter the main groups of cPLA2α inhibitors are described and the problems associated with the development of clinical active drug candidates are discussed. Furthermore, in-vivo data obtained with such compounds in pre-clinical animal models of inflammation will be presented.
S1P Receptor Agonists
Authors: MILLER CRAIG A. 
Published: June 2012

The Sphingosine-1-Phosphate (S1P) family of G-protein coupled receptors (S1P1-5) plays diverse roles under physiological and pathological conditions. Down-regulation of the S1P1 receptor on immune cells causes lymphopenia via sequestration of certain lymphocytes in the secondary lymphoid organs. In the CNS, the S1P1,3,5 receptors promote cell survival and extension. As such, small-molecule intervention along the S1P axis represents a powerful manifold for treatment of immunological diseases such as multiple sclerosis. In 2010 the US FDA approved Finglimod (FTY720/Gilenya®, Novartis) as the first orally bioavailable, disease-modifying agent for the treatment of relapsing-remitting multiple sclerosis. Fingolimod undergoes bioactivation in vivo through invasion of the S1P biosynthetic pathway to a phosphate metabolite, which is an active agonist against four of the five known S1P receptors, thereby eliciting the immunomodulary and CNS protective effects in man.
The considerable success of Fingolimod has generated intense interest in the pharmaceutical industry to develop second-generation S1P receptor agonists with improved safety, efficacy or convenience. This effort has been challenged by deriving various constellations of selectivities, solubility, pharmacokinetic half-lives and in some cases blood-brain barrier penetrability for a phospholipid receptor target that is opposed to compounds with drug-like properties. The various approaches to overcome these challenges as well as the current understanding of S1P receptor biology will be discussed in this chapter.
De-perturbative corrections for charge-stabilized double ionization potential equation-of-motion coupled-cluster method
Authors: Kuś Tomasz , Krylov Anna I. 
Published: June 2012

Charge stabilization improves the numeric performance of double ionization potential equation-of-motion (EOM-DIP) method when using unstable (autoionizing) dianion references. However, the stabilization potential introduces an undesirable perturbation to the target states’ energies. Here we introduce and benchmark two approaches for removing the perturbation caused by the stabilization. The benchmark calculations of excitation energies in selected diradicals illustrate that the so-called core correction based on evaluating the perturbation in a small basis set is robust and yields reliable EOM-DIP values, i.e., the errors of 0.0–0.3 eV against a similar-level coupled-cluster approach.
Communication: Probing non-equilibrium vibrational relaxation pathways of highly excited C≡N stretching modes following ultrafast back-electron transfer
Authors: Lynch Michael S. , Slenkamp Karla M. , Khalil Munira 
Published: June 2012

Fifth-order nonlinear visible-infrared spectroscopy is used to probe coherent and incoherent vibrational energy relaxation dynamics of highly excited vibrational modes indirectly populated via ultrafast photoinduced back-electron transfer in a trinuclear cyano-bridged mixed-valence complex. The flow of excess energy deposited into four C≡N stretching (νCN) modes of the molecule is monitored by performing an IR pump-probe experiment as a function of the photochemical reaction (τvis). Our results provide experimental evidence that the nuclear motions of the molecule are both coherently and incoherently coupled to the electronic charge transfer process. We observe that intramolecular vibrational relaxation dynamics among the highly excited νCN modes change significantly en route to equilibrium. The experiment also measures a 7 cm−1 shift in the frequency of a ∼57 cm−1 oscillation reflecting a modulation of the coupling between the probed high-frequency νCN modes for τvis &lt; 500 fs.