bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer
Authors: Morse Michael A , Garst Jennifer , Osada Takuya , Khan Shubi , Hobeika Amy , Clay Timothy M , Valente Nancy , Shreeniwas Revati , Sutton Mary Ann , Delcayre Alain , Hsu Di-Hwei , Le Pecq Jean-Bernard , Lyerly H Kim 
Published: February 2005

Abstract
Background
There is a continued need to develop more effective cancer immunotherapy strategies. Exosomes, cell-derived lipid vesicles that express high levels of a narrow spectrum of cell proteins represent a novel platform for delivering high levels of antigen in conjunction with costimulatory molecules. We performed this study to test the safety, feasibility and efficacy of autologous dendritic cell (DC)-derived exosomes (DEX) loaded with the MAGE tumor antigens in patients with non-small cell lung cancer (NSCLC).

Methods
This Phase I study enrolled HLA A2+ patients with pre-treated Stage IIIb (N = 4) and IV (N = 9) NSCLC with tumor expression of MAGE-A3 or A4. Patients underwent leukapheresis to generate DC from which DEX were produced and loaded with MAGE-A3, -A4, -A10, and MAGE-3DPO4 peptides. Patients received 4 doses of DEX at weekly intervals.

Results
Thirteen patients were enrolled and 9 completed therapy. Three formulations of DEX were evaluated; all were well tolerated with only grade 1–2 adverse events related to the use of DEX (injection site reactions (N = 8), flu like illness (N = 1), and peripheral arm pain (N = 1)). The time from the first dose of DEX until disease progression was 30 to 429+ days. Three patients had disease progression before the first DEX dose. Survival of patients after the first DEX dose was 52–665+ days. DTH reactivity against MAGE peptides was detected in 3/9 patients. Immune responses were detected in patients as follows: MAGE-specific T cell responses in 1/3, increased NK lytic activity in 2/4.

Conclusion
Production of the DEX vaccine was feasible and DEX therapy was well tolerated in patients with advanced NSCLC. Some patients experienced long term stability of disease and activation of immune effectors
Fructose, insulin resistance, and metabolic dyslipidemia
Authors: Basciano Heather , Federico Lisa , Adeli Khosrow 
Published: February 2005

Abstract
Obesity and type 2 diabetes are occurring at epidemic rates in the United States and many parts of the world. The "obesity epidemic" appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in the amount of dietary fructose consumption from high intake of sucrose and high fructose corn syrup, a common sweetener used in the food industry. A high flux of fructose to the liver, the main organ capable of metabolizing this simple carbohydrate, perturbs glucose metabolism and glucose uptake pathways, and leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG) synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism. These metabolic disturbances appear to underlie the induction of insulin resistance commonly observed with high fructose feeding in both humans and animal models. Fructose-induced insulin resistant states are commonly characterized by a profound metabolic dyslipidemia, which appears to result from hepatic and intestinal overproduction of atherogenic lipoprotein particles. Thus, emerging evidence from recent epidemiological and biochemical studies clearly suggests that the high dietary intake of fructose has rapidly become an important causative factor in the development of the metabolic syndrome. There is an urgent need for increased public awareness of the risks associated with high fructose consumption and greater efforts should be made to curb the supplementation of packaged foods with high fructose additives. The present review will discuss the trends in fructose consumption, the metabolic consequences of increased fructose intake, and the molecular mechanisms leading to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia.
Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity
Authors: Lundberg Karin , Nijenhuis Suzanne , Vossenaar Erik R , Palmblad Karin , van Venrooij Walter J , Klareskog Lars , Zendman AJW , Harris Helena Erlandsson 
Published: February 2005

AbstractAutoantibodies directed against citrulline-containing proteins have an impressive specificity of nearly 100% in patients with rheumatoid arthritis and have been suggested to be involved in the disease pathogenesis. The targeted epitopes are generated by a post-translational modification catalysed by the calcium-dependent enzyme peptidyl arginine deiminase (PAD), which converts positively charged arginine to polar but uncharged citrulline. The aim of this study was to explore the effects of citrullination on the immunogenicity of autoantigens as well as on potential arthritogenicity. Thus, immune responses to citrullinated rat serum albumin (Cit-RSA) and to unmodified rat serum albumin (RSA) were examined as well as arthritis development induced by immunisation with citrullinated rat collagen type II (Cit-CII) or unmodified CII. In addition, to correlate the presence of citrullinated proteins and the enzyme PAD4 with different stages of arthritis, synovial tissues obtained at different time points from rats with collagen-induced arthritis were examined immunohistochemically. Our results demonstrate that citrullination of the endogenous antigen RSA broke immunological tolerance, as was evident by the generation of antibodies directed against the modified protein and cross-reacting with the native protein. Furthermore we could demonstrate that Cit-CII induced arthritis with higher incidence and earlier onset than did the native counterpart. Finally, this study reveals that clinical signs of arthritis precede the presence of citrullinated proteins and the enzyme PAD4. As disease progressed into a more severe and chronic state, products of citrullination appeared specifically in the joints. Citrullinated proteins were detected mainly in extracellular deposits but could also be found in infiltrating cells and on the cartilage surface. PAD4 was detected in the cytoplasm of infiltrating mononuclear cells, from day 21 after immunisation and onwards. In conclusion, our data reveal the potency of citrullination to break tolerance against the self antigen RSA and to increase the arthritogenic properties of the cartilage antigen CII. We also show that citrullinated proteins and the enzyme PAD4 are not detectable in healthy joints, and that the appearance and amounts in arthritic joints of experimental animals are correlated with the severity of inflammation.
The P2X7receptor is a candidate product of murine and human lupus susceptibility loci: a hypothesis and comparison of murine allelic products
Authors: Elliott James I , McVey John H , Higgins Christopher F 
Published: February 2005

AbstractSystemic lupus erythematosus and its murine equivalent, modelled in the New Zealand Black and New Zealand White (NZB × NZW)F1 hybrid strain, are polygenic inflammatory diseases, probably reflecting an autoimmune response to debris from cells undergoing programmed cell death. Several human and murine loci contributing to disease have been defined. The present study asks whether the proinflammatory purinergic receptor P2X7, an initiator of a form of programmed cell death known as aponecrosis, is a candidate product of murine and human lupus susceptibility loci. One such locus in (NZB × NZW)F1 mice is lbw3, which is situated at the distal end of NZW chromosome 5. We first assess whether NZB mice and NZW mice carry distinct alleles of the P2RX7 gene as expressed by common laboratory strains, which differ in sensitivity to ATP stimulation. We then compare the responses of NZB lymphocytes, NZW lymphocytes and (NZB × NZW)F1 lymphocytes to P2X7 stimulation. NZB and NZW parental strains express the distinct P2X7-L and P2X7-P alleles of P2RX7, respectively, while lymphocytes from these and (NZB × NZW)F1 mice differ markedly in their responses to P2X7 receptor stimulation. NZB mice and NZW mice express functionally distinct alleles of the proinflammatory receptor, P2X7. We show that current mapping suggests that murine and human P2RX7 receptor genes lie within lupus susceptibility loci lbw3 and SLEB4, and we argue that these encode a product with the functional characteristics consistent with a role in lupus. Furthermore, we argue that aponecrosis as induced by P2X7 is a cell death mechanism with characteristics that potentially have particular relevance to disease pathogenesis.
Microvascular permeability during experimental human endotoxemia: an open intervention study
Authors: van Eijk Lucas TGJ , Pickkers Peter , Smits Paul , Broek Wim van den , Bouw Martijn PWJM , van der Hoeven Johannes G 
Published: February 2005

Abstract
Introduction
Septic shock is associated with increased microvascular permeability. As a model for study of the pathophysiology of sepsis, endotoxin administration to humans has facilitated research into inflammation, coagulation and cardiovascular effects. The present study was undertaken to determine whether endotoxin administration to human volunteers can be used as a model to study the sepsis-associated increase in microvascular permeability.

Methods
In an open intervention study conducted in a university medical centre, 16 healthy volunteers were evaluated in the research unit of the intensive care unit. Eight were administered endotoxin intravenously (2 ng/kg Escherichia coli O113) and eight served as control individuals. Microvascular permeability was assessed before and 5 hours after the administration of endotoxin (n = 8) or placebo (n = 8) by three different methods: transcapillary escape rate of I125-albumin; venous occlusion strain-gauge plethysmography to determine the filtration capacity; and bioelectrical impedance analysis to determine the extracellular and total body water.

Results
Administration of endotoxin resulted in the expected increases in proinflammatory cytokines, temperature, flu-like symptoms and cardiovascular changes. All changes were significantly different from those in the control group. In the endotoxin group all microvascular permeability parameters remained unchanged from baseline: transcapillary escape rate of I125-albumin changed from 7.2 ± 0.6 to 7.7 ± 0.9%/hour; filtration capacity changed from 5.0 ± 0.3 to 4.2 ± 0.4 ml/min per 100 ml mmHg × 10-3; and extracellular/total body water changed from 0.42 ± 0.01 to 0.40 ± 0.01 l/l (all differences not significant).

Conclusion
Although experimental human endotoxaemia is frequently used as a model to study sepsis-associated pathophysiology, an endotoxin-induced increase in microvascular permeability in vivo could not be detected using three different methods. Endotoxin administration to human volunteers is not suitable as a model in which to study changes in microvascular permeability.
Uneven distribution of ventilation in acute respiratory distress syndrome
Authors: Rylander Christian , Tylén Ulf , Rossi-Norrlund Rauni , Herrmann Peter , Quintel Michael , Bake Björn 
Published: February 2005

Abstract
Introduction
The aim of this study was to assess the volume of gas being poorly ventilated or non-ventilated within the lungs of patients treated with mechanical ventilation and suffering from acute respiratory distress syndrome (ARDS).

Methods
A prospective, descriptive study was performed of 25 sedated and paralysed ARDS patients, mechanically ventilated with a positive end-expiratory pressure (PEEP) of 5 cmH2O in a multidisciplinary intensive care unit of a tertiary university hospital. The volume of poorly ventilated or non-ventilated gas was assumed to correspond to a difference between the ventilated gas volume, determined as the end-expiratory lung volume by rebreathing of sulphur hexafluoride (EELVSF6), and the total gas volume, calculated from computed tomography images in the end-expiratory position (EELVCT). The methods used were validated by similar measurements in 20 healthy subjects in whom no poorly ventilated or non-ventilated gas is expected to be found.

Results
EELVSF6 was 66% of EELVCT, corresponding to a mean difference of 0.71 litre. EELVSF6 and EELVCT were significantly correlated (r2 = 0.72; P < 0.001). In the healthy subjects, the two methods yielded almost identical results.

Conclusion
About one-third of the total pulmonary gas volume seems poorly ventilated or non-ventilated in sedated and paralysed ARDS patients when mechanically ventilated with a PEEP of 5 cmH2O. Uneven distribution of ventilation due to airway closure and/or obstruction is likely to be involved.
Flexible Hexagonal Tube Framework of a New Nickel Complex Assembled from Intermolecular Hydrogen Bonds
Authors: Kondo Mitsuru , Iwase Takahiro , Fuwa Yumiko , Horiba Tomonori , Miyazawa Makoto , Naito Tetsuyoshi , Maeda Kenji , Yasue Sachie , Uchida Fumio 
Published: February 2005

Abstract
A new nickel tubular framework compound, [Ni(ima)2(MeOH)2]·2MeOH (where ima = 4-imidazoleacetato) has been synthesized, in which the nonmethanolated complex, [Ni(ima)2], selectively reacts with methanol to reconstruct the initial porous framework, which can then incorporate other guest molecules.
Preparation of Aligned Amorphous Silica Nanowires
Authors: Xu Yajie , Cao Chuanbao , Zhang Bing , Zhu Hesun 
Published: February 2005

Abstract
Highly aligned amorphous silica nanowires were prepared on silicon substrate. The products were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), and selected-area electron diffraction (SAED). The photoluminescence (PL) spectrum of silica nanowires showed strong blue emission peaked at 401 and 440 nm under 274 nm excitation wavelength. The growth mechanism of the nanowires was proposed.
Enzymatic Synthesis of Gold Nanoparticles Wrapped by Glucose Oxidase
Authors: Yasui Kei , Kimizuka Nobuo 
Published: February 2005

Abstract
An enzymatic synthesis route to protein-wrapped gold nanoparticles is developed. Glucose oxidase (GOD) reduces Au(III) ion in the presence of β-d-glucose, and stable gold nanoparticles with average diameter of 14.5 nm are formed. FT-IR spectra, zeta potential and CD spectra of purified nanoparticles indicate that they are stabilized by the adsorbed protein layer.
Quaternary Ammonium Dendrimers as Lewis Base Catalysts for Mukaiyama–Aldol Reaction
Authors: Mizugaki Tomoo , Hetrick Casey E , Murata Makoto , Ebitani Kohki , Amiridis Michael D , Kaneda Kiyotomi 
Published: February 2005

Abstract
Surface-alkylated poly(propylene imine) dendrimer was treated with methyl iodide to afford quaternarized ammonium iodide dendrimer. The quaternarized dendrimer catalyzed the Mukaiyama–Aldol reaction of trimethylsilyl acetal with various aldehydes as a Lewis base in apolar toluene solvent.
Fluorous Glycopeptide Synthesis without Protection of Sugar Hydroxy Groups
Authors: Mizuno Mamoru , Goto Kohtaro , Miura Tsuyoshi 
Published: February 2005

Abstract
The synthesis of a glycopeptide was easily achieved by an Fmoc-strategy based on fluorous chemistry. In this study, hCG(β12-16) having an N-acetylglucosamine was synthesized in good yield using Fmoc-Asn(GlcNAc)-OH without protection of the sugar hydroxy groups by the dimethylphosphinothioic mixed anhydride (Mpt-MA) method. Each synthetic intermediate was able to be easily purified by simple fluorous-organic solvent extraction and monitored by TLC, NMR, and MS.
Synthesis of Porous Nickel Oxide Nanofiber
Authors: Nakasa Akihiko , Suzuki Eiji , Usami Hisanao , Fujimatsu Hitoshi 
Published: February 2005

Abstract
Porous nickel oxide (NiO) nanofibers, structured with and composed of linearly oriented NiO nanoparticles, were synthesized via a simple method using a solution containing ethanol, H2O, NiCl2, and P123 (Pluronic P123, a triblock copolymer H(OCH2CH2)20(OCH(CH3)CH2)70(OCH2)20OH). By adjusting the concentration of P123, this method allows for the control of the fiber morphology and the nanoparticle size.
The simulation of the diurnal cycle of convective precipitation over land in a global model
Authors: Bechtold P. , Chaboureau J.‐P. , Beljaars A. , Betts A. K. , Köhler M. , Miller M. , Redelsperger J.‐L. 
Published: February 2005

AbstractIn the context of the European Cloud Systems project, the problem of the simulation of the diurnal cycle of convective precipitation over land is addressed with the aid of cloud‐resolving (CRM) and single‐column (SCM) model simulations of an idealized midlatitude case for which observations of large‐scale and surface forcing are available. The CRM results are compared to different versions of the European Centre for Medium‐Range Weather Forecasts (ECMWF) convection schemes using different convective trigger procedures and convective closures. In the CRM, maximum rainfall intensity occurs at 15 h (local time). In this idealized midlatitude case, most schemes do not reproduce the afternoon precipitation peak, as (i) they cannot reproduce the gradual growth (typically over 3 hours) of the deep convective cloud layer and (ii) they produce a diurnal cycle of precipitation that is in phase with the diurnal cycle of the convective available potential energy (CAPE) and the convective inhibition (CIN), consistent with the parcel theory and CAPE closure used in the bulk mass‐flux scheme. The scheme that links the triggering to the large‐scale vertical velocity gets the maximum precipitation at the right time, but this may be artificial as the vertical velocity is enforced in the single‐column context.The study is then extended to the global scale using ensembles of 72‐hour global forecasts at resolution T511 (40 km), and long‐range single 40‐day forecasts at resolution T159 (125 km) with the ECMWF general‐circulation model. The focus is on tropical South America and Africa where the diurnal cycle is most pronounced. The forecasts are evaluated against analyses and observed radiosonde data, as well as observed surface and satellite‐derived rainfall rates. The ECMWF model version with improved convective trigger produces the smallest biases overall. It also shifts the rainfall maximum to 12 h compared to 9.5 h in the original version. In contrast to the SCM, the vertical‐velocity‐dependent trigger does not further improve the phase of the diurnal cycle. However, further work is necessary to match the observed 15 h precipitation peak. Copyright © 2004 Royal Meteorological Society
The sensitivity of a GCM's marine stratocumulus to cloud‐top entrainment
Authors: Lock A. P. 
Published: February 2005

AbstractIt appears that the Met Office general‐circulation model (GCM) represents stratocumulus over the northeast subtropical Pacific Ocean quite accurately—the mean cloud cover is realistically high, the observed mean and diurnal cycle of liquid‐water path is well represented and the capping inversion is at a reasonable height. This suggests that the boundary‐layer thermodynamic budget must also be well modelled. However, one of the dominant terms in this budget is cloud‐top entrainment, which is parametrized explicitly in this model, and is still the subject of much debate in the literature. In order to quantify the sensitivity of the GCM to this parametrization, the results of simulations applying three perturbations of entrainment formulation are presented. One change, to the enhancement of entrainment in the buoyancy‐reversal regime, is found to have little impact. The other two led to a significant reduction of the cloudiness in the stratocumulus area, giving worse agreement with observations. The first of these was to increase the parametrized entrainment rate by a factor of two. The second was to remove the coupling of the entrainment fluxes to the radiative and resolved advective fluxes, an aspect of the implementation previously found necessary to prevent serious numerical errors which generated spurious additional entrainment. It is further hypothesized that the numerical errors can be associated with a signal in the surface heat fluxes in the north‐east Pacific stratocumulus area. This signal can be seen in many other GCMs, suggesting that numerical problems associated with mixing across sharp inversions may be prevalent. © Crown copyright, 2004.
A buoyancy‐based mixing‐length proposal for cloudy boundary layers
Authors: Sáanchez E. , Cuxart J. 
Published: February 2005

AbstractThe parametrization of boundary‐layer clouds is approached here using a turbulence–kinetic energy closure, in conservative variables for non‐precipitating processes and through a new proposal for the turbulence mixing length. A subgrid condensation scheme able to treat partially saturated conditions in a model grid cell is also necessary. An extension of the buoyancy‐based Bougeault–Lacarrère mixing length is proposed, to take into account moist processes, and specifically the effects of phase changes. The asymmetry between upward and downward mixing processes is also considered for partial cloudiness conditions. The new proposal is tested for stratocumulus‐capped marine boundary layers and for shallow cumulus convection, both over land and sea. The validation ismade against large‐eddy simulation results obtained from model intercomparison cases, for stationary regimes as a first step, and then for the diurnal evolution of marine stratocumulus and shallow convection over land. Copyright © 2004 Royal Meteorological Society
The diurnal cycle of shallow cumulus clouds over land: A single‐column model intercomparison study
Authors: Lenderink Geert , Siebesma A. PIER , Cheinet Sylvain , Irons Sarah , Jones Colin G. , Marquet Pascal , üLLER Frank M , Olmeda Dolores , Calvo Javier , Sánchez Enrique , Soares Pedro M. M. 
Published: February 2005

AbstractAn intercomparison study for single‐column models (SCMs) of the diurnal cycle of shallow cumulus convection is reported. The case, based on measurements at the Atmospheric Radiation Measurement program Southern Great Plains site on 21 June 1997, has been used in a large‐eddy simulation intercomparison study before. Results of the SCMs reveal the following general deficiencies: too large values of cloud cover and cloud liquid water, unrealistic thermodynamic profiles, and high amounts of numerical noise. Results are also strongly dependent on vertical resolution.These results are analysed in terms of the behaviour of the different parametrization schemes involved: the convection scheme, the turbulence scheme, and the cloud scheme. In general the behaviour of the SCMs can be grouped in two different classes: one class with too strong mixing by the turbulence scheme, the other class with too strong activity by the convection scheme. The coupling between (subcloud) turbulence and the convection scheme plays a crucial role. Finally, (in part) motivated by these results several models have been successfully updated with new parametrization schemes and/or their present schemes have been successfully modified. © Royal Meteorological Society, 2004. S. Irons's contribution is Crown copyright