bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resurrecting an extinct salmon evolutionarily significant unit: archived scales, historical DNA and implications for restoration
Authors: IWAMOTO ERIC M. , MYERS JAMES M. , GUSTAFSON RICHARD G. 
Published: January 2012

AbstractArchival scales from 603 sockeye salmon (Oncorhynchus nerka), sampled from May to July 1924 in the lower Columbia River, were analysed for genetic variability at 12 microsatellite loci and compared to 17 present‐day O. nerka populations—exhibiting either anadromous (sockeye salmon) or nonanadromous (kokanee) life histories—from throughout the Columbia River Basin, including areas upstream of impassable dams built subsequent to 1924. Statistical analyses identified four major genetic assemblages of sockeye salmon in the 1924 samples. Two of these putative historical groupings were found to be genetically similar to extant evolutionarily significant units (ESUs) in the Okanogan and Wenatchee Rivers (pairwise FST = 0.004 and 0.002, respectively), and assignment tests were able to allocate 77% of the fish in these two historical groupings to the contemporary Okanogan River and Lake Wenatchee ESUs. A third historical genetic grouping was most closely aligned with contemporary sockeye salmon in Redfish Lake, Idaho, although the association was less robust (pairwise FST = 0.060). However, a fourth genetic grouping did not appear to be related to any contemporary sockeye salmon or kokanee population, assigned poorly to the O. nerka baseline, and had distinctive early return migration timing, suggesting that this group represents a historical ESU originating in headwater lakes in British Columbia that was probably extirpated sometime after 1924. The lack of a contemporary O. nerka population possessing the genetic legacy of this extinct ESU indicates that efforts to reestablish early‐migrating sockeye salmon to the headwater lakes region of the Columbia River will be difficult.
Elevated levels of IFNγ and LIGHT in the spinal cord of patients with sporadic amyotrophic lateral sclerosis
Authors: Aebischer J. , Moumen A. , Sazdovitch V. , Seilhean D. , Meininger V. , Raoul C. 
Published: January 2012

Background:  Amyotrophic lateral sclerosis (ALS) is a paralytic and fatal neurodegenerative disorder caused by the gradual loss of both upper and lower motoneurons. There is compelling evidence from ALS experimental models that neuroinflammation actively contributes to motoneuron damage. We recently proposed that interferon gamma (IFNγ), a potent proinflammatory cytokine, induces motoneuron death by eliciting the activation of the lymphotoxin beta receptor (LT‐βR) through its ligand LIGHT. Here, we explore the pertinence of this non‐cell‐autonomous mechanism in human ALS.Methods:  The levels and expression pattern of IFNγ, LIGHT, and LT‐βR were investigated by Western blot and immunohistochemical analysis in spinal cord of patients with sporadic ALS.Results:  We observed significant increased levels of IFNγ in human ALS spinal cords compared to control cases. We found that large ventral horn neurons as well as glial cells were immunoreactive for IFNγ in sporadic ALS spinal cord. We further observed that LIGHT and LT‐βR were expressed mainly by motoneurons in both ALS and control cases, and while LT‐βR levels remained constant between ALS and control cases, LIGHT levels were increased in human ALS spinal cords.Conclusion:  These findings in sporadic ALS cases, which are consistent with the observation made in ALS experimental models, propose that the IFNγ‐triggered LIGHT/LT‐βR‐mediated death pathway may contribute to human ALS pathogenesis.
High anti‐EBNA‐1 IgG levels are associated with early‐onset myasthenia gravis
Authors: Csuka D. , Banati M. , Rozsa C. , Füst G. , Illes Z. 
Published: January 2012

Background:  Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against the acethylcholine receptor (AchR) of the neuromuscular junction in the majority of patients.Methods:  Here, we examined IgG antibodies against the type 1 nuclear antigen of Epstein‐Barr virus (EBNA‐1) in the sera of 158 patients with MG compared to 184 healthy controls.Results:  Although serum concentration in the sera was not different, high anti‐EBNA‐1 IgG titers (above 90th percentile of the normal values) were more common in the patients (26.6 vs. 16.3%, P = 0.024). In addition, high EBNA‐1 IgG levels occurred more frequently amongst the 94 patients with early‐onset myasthenia gravis (EOMG, 30.8%) as compared to the 64 patients with late‐onset disease (LOMG, 14.1%) (P = 0.021). Using multiple logistic regression, high serum concentration of the anti‐EBNA‐1 IgG antibodies was significantly associated with EOMG (OR: 3.17, P = 0.027), even after adjustment for sex, presence/absence of anti‐AchR antibodies and presence/absence of anti‐Titin antibodies. Out of 39 patients with EOMG, who underwent thymectomy, 18 patients (46%) had thymoma, 6 had thymic hyperplasia (15%), and 15 patients had thymic atrophy (39%); there was no difference comparing EBNA‐1 antibody titers in the sera. As no correlation was found between the titers of anti‐AchR, anti‐Titin, and EBNA‐1 antibodies, a dysregulated heterogeneous B‐cell response was unlikely to be responsible for the elevated levels of EBV‐associated antibody in patients.Conclusions:  In summary, our data suggest that high levels of EBNA‐1 antibodies are more common in MG compared to healthy controls and are especially associated with EOMG.
Antimicrobial Use at the End of Life Among Hospitalized Patients With Advanced Cancer
Authors: Thompson Andrew J. , Silveira Maria J. , Vitale Caroline A. , Malani Preeti N. 
Published: January 2012

Background: We sought to evaluate antimicrobial use among patients with advanced cancer. Methods: Retrospective review of patients experiencing cancer-related death while hospitalized. Results: Among 145 patients, 126 (86.9%) received antimicrobials for a mean of 12.5 ± 12.9 days. 88 (69.8%) of 126 had clinical findings suggestive of infection. Sixty-one patients (48.4%) had positive cultures, the remaining were treated empirically. “Comfort care” was ultimately pursued in 99 (78.5%) of 126; 35 (35.4%) of 99 continued to receive antimicrobials after a transition to comfort care for an average of 1.6 ± 1.1 days. On average, antimicrobials were discontinued <1day prior to death. Conclusion: Antimicrobial use was common among patients with advanced cancer. Even after transition to comfort care, more than one third of patients remained on antimicrobials. The risks and burdens of antimicrobials should be carefully examined when comfort is the stated goal.
Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy
Authors: Fahmueller Yvonne Nadine , Nagel Dorothea , Hoffmann Ralf-Thorsten , Tatsch Klaus , Jakobs Tobias , Stieber Petra , Holdenrieder Stefan 
Published: January 2012

Abstract

Background
Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT.

Methods
Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival.

Results
Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model.

Conclusion
Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy.
Preventing intimal thickening of vein grafts in vein artery bypass using STAT-3 siRNA
Authors: Sun Jiangbin , Zheng Jinhua , Ling Kaitelynne H , Zhao Keyan , Xie Zhongshang , Li Bo , Wang Tiance , Zhu Zhicheng , Patel Amit N , Min Weiping , Liu Kexiang , Zheng Xiufen 
Published: January 2012

Abstract

Background
Proliferation and migration of vascular smooth muscle cells (VSMCs) play a key role in neointimal formation which leads to restenosis of vein graft in venous bypass. STAT-3 is a transcription factor associated with cell proliferation. We hypothesized that silencing of STAT-3 by siRNA will inhibit proliferation of VSMCs and attenuate intimal thickening.

Methods
Rat VSMCs were isolated and cultured in vitro by applying tissue piece inoculation methods. VSMCs were transfected with STAT 3 siRNA using lipofectamine 2000. In vitro proliferation of VSMC was quantified by the MTT assay, while in vivo assessment was performed in a venous transplantation model. In vivo delivery of STAT-3 siRNA plasmid or scramble plasmid was performed by admixing with liposomes 2000 and transfected into the vein graft by bioprotein gel applied onto the adventitia. Rat jugular vein-carotid artery bypass was performed. On day 3 and7 after grafting, the vein grafts were extracted, and analyzed morphologically by haematoxylin eosin (H&E), and assessed by immunohistochemistry for expression of Ki-67 and proliferating cell nuclear antigen (PCNA). Western-blot and reverse transcriptase polymerase chain reaction (RT-PCR) were used to detect the protein and mRNA expression in vivo and in vitro. Cell apoptosis in vein grafts was detected by TUNEL assay.

Results
MTT assay shows that the proliferation of VSMCs in the STAT-3 siRNA treated group was inhibited. On day 7 after operation, a reduced number of Ki-67 and PCNA positive cells were observed in the neointima of the vein graft in the STAT-3 siRNA treated group as compared to the scramble control. The PCNA index in the control group (31.3 ± 4.7) was higher than that in the STAT-3 siRNA treated group (23.3 ± 2.8) (P < 0.05) on 7d. The neointima in the experimental group(0.45 ± 0.04 μm) was thinner than that in the control group(0.86 ± 0.05 μm) (P < 0.05).Compared with the control group, the protein and mRNA levels in the experimental group in vivo and in vitro decreased significantly. Down regulation of STAT-3 with siRNA resulted in a reduced expression of Bcl-2 and cyclin D1. However, apoptotic cells were not obviously found in all grafts on day 3 and 7 post surgery.

Conclusions
The STAT-3 siRNA can inhibit the proliferation of VSMCs in vivo and in vitro and attenuate neointimal formation.
On approximation of asymmetric separators of the n-cube
Authors: Boroński Jan P , Turzański Marian 
Published: January 2012

Abstract
A new combinatorial result intertwined with the Brouwer fixed point theorem for the n-cube is given. This result can be used for any map (f
1, ..., fn): [0, 1]
n
→ [0, 1]
n
to approximate the components of the set {(x
1, . . . , x

n
) ∈ [0, 1]
n
: f

i
(x
1, . . . , x

n
) = x

i
} that separate the n-cube between the i th opposite faces. Equivalently, for maps g : [0, 1]
n
→ ℝ such that g(x)g(y) ≤ 0 for any x ∈ {0} × [0, 1]
n-1and y ∈ {1} × [0, 1]
n-1, one can use the algorithm to approximate the components of g
-1(0) that separate [0, 1]
n
between {0} × [0, 1]
n-1and {1} × [0, 1]
n-1. The methods are based on an earlier result of P. Minc and the present authors and relate to results of several other authors such as Jayawant and Wong, Kulpa and Turzański, and Gale.

Mathematics Subject Classification (2000): Primary 54H25; 54-04; Secondary 55M20; 54F55.
Safety and Efficacy of Everolimus in Adult Patients with Neuroendocrine Tumors
Authors: Oberstein Paul E. , Saif M. Wasif 
Published: January 2012

Neuroendocrine tumors (NETs) consist of a diverse family of tumors which are derived from the neuroendocrine system. Most NETs are well or moderately differentiated tumors with a relatively indolent growth pattern. However, these tumors can cause significant clinical disease due to release of functional products that mediate the carcinoid syndrome and other diverse sequela. They also can grow progressively and cause symptoms from local invasion or distant metastasis. NETs are optimally treated with surgery and somatosatin analogs (SSAs) to control symptoms but are relatively insensitive to systemic chemotherapy. As a result, patients with advanced unresectable NETs have a poor prognosis. In 2011, two targeted therapies, sunitinib and everolimus were approved in the subset of progressive pancreatic NETs (pNETs). Everolimus is an oral inhibitor of the growth stimulatory mTOR pathway. In Phase 2 trials in NETs and pNETs, everolimus was well tolerated and associated with some response and widespread disease stabilization. In follow-up, randomized Phase 3 trials, everolimus was compared to placebo. In the RADIANT-2 trial, everolimus and a somatostatin analog were used in patients with functional NETs and treatment was associated with an an improvement in progression-free survival (PFS). In the RADIANT-3 trial, patients with pNET were randomized to receive everolimus or placebo along with best supportive care. Everolimus was again associated with improvement in PFS compared to placebo and it has been approved by the FDA for patients with progressive pNET. Everolimus is associated with frequent low grade toxicity but is also notable for increased rates of infection as well as non-infectious pneumonitis. mTOR inhibition with everolimus represents a significant advance in the treatment of advanced neuroendocrine tumors.
Kinetic investigation of a solvent‐free, chemoenzymatic reaction sequence towards enantioselective synthesis of a β‐amino acid ester
Authors: Strompen Simon , Weiß Markus , Ingram Thomas , Smirnova Irina , Gröger Harald , Hilterhaus Lutz , Liese Andreas 
Published: January 2012

AbstractA solvent‐free, chemoenzymatic reaction sequence for the enantioselective synthesis of β‐amino acid esters has been kinetically and thermodynamically characterized. The coupled sequence comprises a thermal aza‐Michael addition of cheap starting materials and a lipase catalyzed aminolysis for the kinetic resolution of the racemic ester. Excellent ee values of >99% were obtained for the β‐amino acid ester at 60% conversion. Kinetic constants for the aza‐Michael addition were obtained by straightforward numerical integration of second‐order rate equations and nonlinear fitting of the progress curves. A different strategy had to be devised for the biocatalytic reaction. Initially, a simplified Michaelis–Menten model including product inhibition was developed for the reaction running in THF as an organic solvent. Activity based parameters were used instead of concentrations in order to facilitate the transfer of the kinetic model to the solvent‐free system. Observed solvent effects not accounted for by the use of thermodynamic activities were incorporated into the kinetic model. Enzyme deactivation was observed to depend on the ratio of the applied substrates and also included in the kinetic model. The developed simple model is in very good agreement with the experimental data and allows the simulation and optimization of the solvent‐free process. Biotechnol. Bioeng. 2012; 109:1479–1489. © 2012 Wiley Periodicals, Inc.
Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor
Authors: McCoy R.J. , Jungreuthmayer C. , O'Brien F.J. 
Published: January 2012

AbstractMechanically stimulating cell‐seeded scaffolds by flow‐perfusion is one approach utilized for developing clinically applicable bone graft substitutes. A key challenge is determining the magnitude of stimuli to apply that enhances cell differentiation but minimizes cell detachment from the scaffold. In this study, we employed a combined computational modeling and experimental approach to examine how the scaffold mean pore size influences cell attachment morphology and subsequently impacts upon cell deformation and detachment when subjected to fluid‐flow. Cell detachment from osteoblast‐seeded collagen–GAG scaffolds was evaluated experimentally across a range of scaffold pore sizes subjected to different flow rates and exposure times in a perfusion bioreactor. Cell detachment was found to be proportional to flow rate and inversely proportional to pore size. Using this data, a theoretical model was derived that accurately predicted cell detachment as a function of mean shear stress, mean pore size, and time. Computational modeling of cell deformation in response to fluid flow showed the percentage of cells exceeding a critical threshold of deformation correlated with cell detachment experimentally and the majority of these cells were of a bridging morphology (cells stretched across pores). These findings will help researchers optimize the mean pore size of scaffolds and perfusion bioreactor operating conditions to manage cell detachment when mechanically simulating cells via flow perfusion. Biotechnol. Bioeng. 2012; 109:1583–1594. © 2012 Wiley Periodicals, Inc.
A Facile Synthesis of Dynamic Supramolecular Aggregates of Cucurbit[n]uril (n=5–8) Capped with Gold Nanoparticles in Aqueous Media
Authors: Lee Tung‐Chun , Scherman Oren A. 
Published: January 2012

AbstractSupramolecular capping of cucurbit[n]uril (CB[n]), where n=5–8, by narrowly dispersed gold nanoparticles has been achieved through a facile synthetic route with metastable gold nanoparticles as a labile intermediate. The resultant assemblies were stable in solution, and were found to form dynamic aggregates consisting of a controllable ratio of singly and doubly capped CB[n]. The stability of the system was attributed to the presence of sodium cations bound on the vacant carbonyl portals of the singly capped CB[n] molecules. These dynamically capped CB[n] systems can find potential use in a range of applications varying from ultrasensitive multiplexed in situ sensing to photocatalysis.
Transition Metal Hydrazide‐Based Hydrogen‐Storage Materials: the First Atoms‐In‐Molecules Analysis of the Kubas Interaction
Authors: Skipper Claire V. J. , Hoang Tuan K. A. , Antonelli David M. , Kaltsoyannis Nikolas 
Published: January 2012

AbstractMolecular models of the MH2 binding sites of experimentally characterised amorphous vanadium hydrazide gels are studied computationally using gradient corrected density functional theory, to probe the coordination number of the vanadium in the material and the nature of the interaction between the metal and the H2 molecules. The H2 is found to bind to the vanadium through the Kubas interaction, and the first quantum theory of atoms‐in‐molecules analysis of this type of interaction is reported. Strong correlation is observed between the electron density at the HH bond critical point and the MH2 interaction energy. Four coordinate models give the best reproduction of the experimental data, suggesting that the experimental sites are four coordinate. The VH2 interaction is shown to be greater when the non‐hydrazine based ligand, THF, of the experimental system is altered to a poorer π‐acceptor ligand. Upon altering the metal to Ti or Cr the MH2 interaction energy changes little but the number of H2 which may be bound decreases from four (Ti) to two (Cr). It is proposed that changing the metal from V to Ti may increase the hydrogen storage capacity of the experimental system. A 9.9 wt % maximum storage capacity at the ideal binding enthalpy for room temperature performance is predicted when the Ti metal is combined with a coordination sphere containing 2 hydride ligands.
Electron‐Transfer Reduction of Dinuclear Copper Peroxo and Bis‐μ‐oxo Complexes Leading to the Catalytic Four‐Electron Reduction of Dioxygen to Water
Authors: Tahsini Laleh , Kotani Hiroaki , Lee Yong‐Min , Cho Jaeheung , Nam Wonwoo , Karlin Kenneth D. , Fukuzumi Shunichi 
Published: January 2012

AbstractThe four‐electron reduction of dioxygen by decamethylferrocene (Fc*) to water is efficiently catalyzed by a binuclear copper(II) complex (1) and a mononuclear copper(II) complex (2) in the presence of trifluoroacetic acid in acetone at 298 K. Fast electron transfer from Fc* to 1 and 2 affords the corresponding CuI complexes, which react at low temperature (193 K) with dioxygen to afford the η2:η2‐peroxo dicopper(II) (3) and bis‐μ‐oxo dicopper(III) (4) intermediates, respectively. The rate constants for electron transfer from Fc* and octamethylferrocene (Me8Fc) to 1 as well as electron transfer from Fc* and Me8Fc to 3 were determined at various temperatures, leading to activation enthalpies and entropies. The activation entropies of electron transfer from Fc* and Me8Fc to 1 were determined to be close to zero, as expected for outer‐sphere electron‐transfer reactions without formation of any intermediates. For electron transfer from Fc* and Me8Fc to 3, the activation entropies were also found to be close to zero. Such agreement indicates that the η2:η2‐peroxo complex (3) is directly reduced by Fc* rather than via the conversion to the corresponding bis‐μ‐oxo complex, followed by the electron‐transfer reduction by Fc* leading to the four‐electron reduction of dioxygen to water. The bis‐μ‐oxo species (4) is reduced by Fc* with a much faster rate than the η2:η2‐peroxo complex (3), but this also leads to the four‐electron reduction of dioxygen to water.
Flow‐level performance analysis of a multi‐rate system supporting stream and elastic services
Authors: Gerő B. P. , Pályi P. L. , Rácz S. 
Published: January 2012

SUMMARYWe consider a multi‐rate system where stream and elastic flows receive service. Both the stream and the elastic classes are associated with peak rate limitation. In contrast to the constant bit rate stream flows, the elastic flows tolerate bandwidth compression while in service. Because of the occasional bandwidth compression, the holding time of elastic flows depends on their perceived throughput. Although this model is Markovian under quite non‐restrictive assumptions, the model's state space grows exponentially with the number of traffic classes. The model is not quasi‐reversible, and therefore, it cannot be evaluated by efficient recursive formulae. We propose a method whereby the original state space is mapped to a two‐dimensional one, independently of the number of the stream and the elastic traffic classes. The special structure of the two‐dimensional model allows us to develop an efficient method that approximates the average throughputs of elastic flows. The state space reduction together with the proposed approximation provides a powerful tool for the performance analysis of this model as it allows the approximation of the average throughputs of elastic flows reasonably accurately in large models as well. Copyright © 2012 John Wiley & Sons, Ltd.