bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with transducible phosphopeptide analogues of the small heat shock–related protein, HSP20, after experimental subarachnoid hemorrhage: prevention and reversal of delayed decreases in cerebral perfusion
Authors: Furnish Elizabeth J. , Brophy Colleen M. , Harris Valerie A. , Macomson Samuel , Winger Julia , Head Geoffrey A. , Shaver Ellen G. 
Published: September 2009

Object
Delayed vasospasm is a significant cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Proteomic therapeutics offers a new modality in which biologically active proteins or peptides are transduced into cells via covalent linkage to cell permeant peptides (CPPs). The hypothesis of this study was that either intrathecal or intravenous delivery of a phosphopeptide mimetic of the small heat shock–related protein, HSP20, linked to a CPP, would inhibit delayed decreases in cerebral perfusion after experimental SAH in a rat model.

Methods
This study was conducted in 3 parts: 1) prevention and 2) reversal of delayed decreases in cerebral perfusion via either intrathecal or intravenous administration of a CPP linked to phosphopeptide mimetics of HSP20 (AZX100) and 3) determining the effect of intravenous administration of AZX100 on blood pressure and heart rate. Subarachnoid hemorrhage was induced in rats by endovascular perforation. Subsequently, AZX100 was administered intrathecally via a cisternal catheter or intravenously. Cerebral perfusion was determined by laser Doppler monitoring. Blood pressure was monitored by telemetry in a separate group of naïve animals treated with AZX100 for 24 hours.

Results
The maximal decrease in cerebral perfusion occurred 3 days after SAH. Cisternal administration of AZX100 (0.14–0.57 mg/kg) 24 hours after hemorrhage prevented decreases in cerebral perfusion after SAH. Animals receiving lower doses of AZX100 (0.068 mg/kg) or a scrambled sequence of the active HSP20 peptide linked to CPP developed decreases in cerebral perfusion similar to those seen in control animals. Intravenous administration of AZX100 (1.22 mg/kg) 24 hours after hemorrhage prevented the decreases in cerebral perfusion seen in the controls. Intravenous administration (0.175 mg/kg and 1.22 mg/kg) of AZX100 on Days 2 and 3 after SAH reversed decreases in cerebral perfusion as early as Day 3. There was no impact of AZX100 on blood pressure or heart rate at doses up to 2.73 mg/kg.

Conclusions
Cisternal administration of AZX100 24 hours after hemorrhage prevented decreases in cerebral perfusion. Intravenous administration of AZX100 also prevented and reversed decreases in cerebral perfusion at doses that did not induce hypotension. Transduction of biologically active motifs of downstream regulators like HSP20 represents a potential novel treatment for SAH.
Improvement in intensive care unit outcomes in patients with subarachnoid hemorrhage after initiation of neurointensivist co-management
Authors: Josephson S. Andrew , Douglas Vanja C. , Lawton Michael T. , English Joey D. , Smith Wade S. , Ko Nerissa U. 
Published: September 2009

Object
Neurointensivists are specialists trained to manage all aspects of the intensive care unit (ICU) stay of neurologically ill patients. No study to date has examined the role of neurointensivists specifically in subarachnoid hemorrhage (SAH) management. This study examined the use of a team-based neurointensivist co-management approach.

Methods
The authors reviewed all cases involving patients with SAH admitted to the neurosurgical service during a period of more than 4 years. A comparison was made between those patients admitted before and those admitted after the initiation of a mandatory neurointensivist co-management strategy. The primary outcome examined was length of ICU stay. Secondary outcomes included in-hospital mortality, ventriculoperitoneal shunt placement, and other complications such as fever, antibiotic use, pressor utilization, and ventilator-associated pneumonia.

Results
A total of 512 patients were included, 216 prior to and 296 after the initiation of neurointensivist comanagement. Length of ICU stay was significantly decreased after the initiation of neurointensivist co-management (mean 12.4 vs 10.9 days, p = 0.02), even after adjusting for demographic characteristics and admission Hunt and Hess grade. The percentage of patients requiring a ventriculoperitoneal shunt significantly decreased after initiation of the co-management approach (23.0 vs 11.5%, p = 0.001), but in-house mortality was unaffected.

Conclusions
Initiation of a strategy of routine involvement of a neurointensivist, charged with managing all aspects of the patients' care, resulted in a significantly reduced length of ICU stay for neurosurgical SAH patients. This team-based approach, using neurointensivists to manage neurosurgical SAH patients, merits further study as a successful model of care.
Effect of Monochromatic Induced Aberrations on Visual Performance Measured by Adaptive Optics Technology
Authors: Rouger Hélène , Benard Yohann , Legras Richard 
Published: September 2009

Purpose:
The two objectives were 1) to measure visual acuity (VA) and contrast sensitivity (CS) losses induced by various amounts of individual Zernike aberrations, and 2) to examine the accuracy of image quality metrics in predicting these visual performance losses.

Methods:

Monocular 10 cycles/degree (cpd) and 25 cpd CS and high- and low-contrast VA were measured when introducing individual Zernike aberrations in four patients dynamically corrected using a CRX1 adaptive optics system (Imagine Eyes) and a 5.5-mm pupil. Seven levels (0, ±0.1, ±0.3, and ±0.9
μ
m) of astigmatism, spherical aberration, coma, and trefoil and four levels of defocus were induced. Several image quality metrics based on the radially averaged modulation transfer function (rMTF) and optical transfer function (rOTF) calculations were computed to attempt to predict the losses in VA and CS.

Results:

Modes near the center and at the top of the Zernike pyramid decreased VA significantly more than modes near the edge or at the bottom of the pyramid. The measured CS losses were reasonably correlated to the rMTF calculated at 10 cpd (R
2
=0.87) and 25 cpd (R
2
=0.75). The high-contrast VA degradations were also reasonably predicted (R
2
=0.85) by the intersection between the rMTF and the neural contrast threshold function. The low-contrast VA losses were also well predicted (R
2
=0.88) by three rMTF-based metrics.

Conclusions:
Image quality metrics based on wavefront aberration measurements were able to predict the impact of individual Zernike aberrations on CS and VA.
Organisationally relevant variables and Keyes's Mental Health Continuum Scale: An exploratory study
Authors: Strümpfer Deo J.W. , Hardy Anneli , De Villiers Joan S. , Rigby Susan 
Published: September 2009

In an exploratory study on a sample of convenience (n = 165), 11 self-report variables with presumed organisational relevance were related, as predictors, to the three subscores and summed score of the Keyes (2005a, 2005b; 2007) Mental Health Continuum scale (long form). Keyes's scale was administered five to seven days after the first set of scales. The predictor scores were reduced to three factorial scores, labelled positive orientation, negative orientation and positive striving. When classified thus, the predictor variables showed significant and meaningful relationships with some or all of the Keyes subscores and the total score, although few reached medium effect sizes.
The Conserved Glu in the Cyclotide Cycloviolacin O2 Has a Key Structural Role
Authors: Göransson Ulf , Herrmann Anders , Burman Robert , Haugaard‐Jönsson Linda M. , Rosengren K. Johan 
Published: September 2009

AbstractCyclotides are a large family of plant peptides that are characterised by a head‐to‐tail circular backbone and three disulfide bonds that are arranged in a cystine knot. This unique structural feature, which is referred to as a cyclic cystine knot, gives the cyclotides remarkable stability against chemical and biological degradation. In addition to their natural function as insecticides for plant defence, the cyclotides have a range of bioactivities with pharmaceutical relevance, including cytotoxicity against cancer cell lines. A glutamic acid residue, aside from the invariable disulfide array, is the most conserved feature throughout the cyclotide family, and it has recently been shown to be crucial for biological activity. Here we have used solution‐state NMR spectroscopy to determine the three‐dimensional structures of the potent cytotoxic cyclotide cycloviolacin O2, and an inactive analogue in which this conserved glutamic acid has been methylated. The structures of the peptides show that the glutamic acid has a key structural role in coordinating a set of hydrogen bonds in native cycloviolacin O2; this interaction is disrupted in the methylated analogue. The proposed mechanism of action of cyclotides is membrane disruption and these results suggest that the glutamic acid is linked to cyclotide function by stabilising the structure to allow efficient aggregation in membranes, rather than in a direct interaction with a target receptor.
Improvement of Flowability of Fine Cohesive Powders by Flow Additives
Authors: Tomas J. , Kleinschmidt S. 
Published: September 2009

AbstractMost minerals and concentrates, auxiliaries, agricultural and synthetic particulate solid products are produced with particle sizes of less than 100 μm. These fine powders show similar problematic product properties. Their interparticle adhesion forces, especially van der Waals forces, exceed the gravitational forces by orders of magnitude. Thus, the trouble‐free treatment of these products presents large problems as well as scientific and technological challenges. The physical properties of such materials, especially flowability, are essential for many industrial applications including product generation, processing, application and consumption, e.g., in the pharmaceutical, chemical, food and manufacturing industries or plant engineering. In recent decades, one of the most frequently used solutions to this problem has been to add small amounts of flow additives that improve the flowability of these fine cohesive powders. This paper provides an overview of the physico‐chemically active principles of flow additives, model approaches and useful flowability evaluation methods. The efficiency of several flow additives, i.e., nanoparticles and surfactants, is critically discussed by the provision of selected test results from the literature. Conclusions are drawn with respect to the application of this flow additive method in process industries.
Supercritical Antisolvent Particle Precipitation: In Situ Optical Investigations
Authors: Braeuer A. , Dowy S. , Schatz R. , Rossmann M. , Schluecker E. , Leipertz A. 
Published: September 2009

AbstractThe manner in which the presence of a solute can affect the mixing behavior of a solute, solvent and antisolvent in a supercritical antisolvent (SAS) micronization process is demonstrated. The mixing behavior was analyzed by applying a two‐dimensional (2D) Raman scattering technique. Mole fraction and partial density distributions were measured for the CO2 antisolvent. The results originating from the optical investigations were correlated with the particle results. The experiments cover the variation of the solute concentration at fixed operating conditions of 10 MPa and 40 °C.
A flexible high‐performance Lattice Boltzmann GPU code for the simulations of fluid flows in complex geometries
Authors: Bernaschi Massimo , Fatica Massimiliano , Melchionna Simone , Succi Sauro , Kaxiras Efthimios 
Published: September 2009

AbstractWe describe the porting of the Lattice Boltzmann component of MUPHY, a multi‐physics/scale simulation software, to multiple graphics processing units using the Compute Unified Device Architecture. The novelty of this work is the development ofad hoctechniques for optimizing the indirect addressing that MUPHY uses for efficient simulations of irregular domains. Copyright © 2009 John Wiley & Sons, Ltd.
Targeted therapy to the IL‐2R using diphtheria toxin and caspase‐3 fusion proteins modulates Treg and ameliorates inflammatory colitis
Authors: Yarkoni Shai , Sagiv Yuval , Kaminitz Ayelet , Farkas Daniel L. , Askenasy Nadir 
Published: September 2009

AbstractPathogenic lymphocytes in the enteric wall of inflammatory bowel disease patients display various abnormalities, including reduced sensitivity to apoptosis. We evaluated a therapeutic approach to elimination of cytotoxic cells, using two IL‐2 fusion proteins, a diphtheria toxin (IL2‐DT) and a caspase‐3 (IL2‐cas) conjugate. In models of acute (dextran sodium sulfate and trinitrobenzene sulfonic acid) and chronic (dextran sodium sulfate) toxic colitis, therapeutic doses of the fusion proteins improved survival and prevented colon shortening. While both chimeric proteins eradicated CD4+CD25+Foxp3+ T cells in mesenteric LN, IL2‐DT caused severe lymphopenia. In contrast, IL2‐cas was equally protective and increased fractional expression of Foxp3. Similar effects of the fusion proteins were observed in healthy mice: IL2‐DT caused lymphopenia and IL2‐cas increased fractional expression of FoxP3. The fusion proteins induced apoptosis in CD25+ T cells in vitro, with lower toxicity of IL2‐cas to Foxp3+ T cells. These data infer that targeted depletion of cells expressing the IL‐2 receptor has therapeutic potential in models of inflammatory colitis, despite depletion of CD25+ Treg. The IL2‐cas fusion protein is particularly relevant to inflammatory bowel disease, as direct internalization of toxic moieties overcomes multiple pathways of resistance to apoptosis of colitogenic T cells.
Redistribution of cadmium, copper, lead, nickel, and zinc among soil fractions in a contaminated calcareous soil after application of nitrogen fertilizers
Authors: Jalali Mohsen , Moharami Somaieh 
Published: September 2009

AbstractThis study was conducted to evaluate the redistribution of the heavy metals Cd, Cu, Pb, Ni, and Zn among different soil fractions by N fertilizers. In a lab experiment, soil columns were leached with distilled water, KNO3, NaNO3, NH4NO3, or Ca(NO3)2 · 4H2O. After leaching, soil samples were sequentially extracted for exchangeable (EXCH), carbonate (CARB), organic‐matter (OM), Mn oxide (MNO), Fe oxide (FEO), and residual (RES) fractions. Distilled water significantly increased the concentrations of Cd and Ni in EXCH fraction, while concentration of Cu and Zn did not change significantly. Application of KNO3, NaNO3, NH4NO3, or Ca(NO3)2 · 4H2O significantly increased the concentrations of Cd and Zn in EXCH fraction, while concentration of Pb and Ni was decreased. Application of all fertilizers caused an increase of Cu in the OM fraction. Moreover, leaching with these solutions significantly increased Cd [except in Ca(NO3)2 · 4H2O], Cu, and Zn concentrations in the CARB fraction, while Pb and Ni concentrations were decreased. With application of all leaching solutions, Zn in the EXCH, CARB, FEO, and MNO fractions was significantly increased, while Zn in the OM fraction did not change. The mobility index indicated that Ca(NO3)2 · 4H2O increased the mobility of Cd, Cu, and Zn in the soil, whereas NaNO3 decreased the mobility of Pb and Ni in the soil. The mobility index of Pb decreased by all leaching solutions. Thus, these results suggest that applying N fertilizers may change heavy‐metal fractions in contaminated calcareous soil and possibly enhance metal mobility and that N‐fertilization management therefore may need modification.
Reconstructing ENSO: the influence of method, proxy data, climate forcing and teleconnections
Authors: Wilson Rob , Cook Edward , D'Arrigo Rosanne , Riedwyl Nadja , Evans Michael N. , Tudhope Alexander , Allan Rob 
Published: September 2009

AbstractIn this study we compare three newly developed independent NINO3.4 sea surface temperature (SST) reconstructions using data from (1) the central Pacific (corals), (2) the TexMex region of the USA (tree rings) and (3) other regions in the Tropics (corals and an ice core) which are teleconnected with central Pacific SSTs in the 20th century. Although these three reconstructions are strongly calibrated and well verified, inter‐proxy comparison shows a significant weakening in inter‐proxy coherence in the 19th century. This breakdown in common signal could be related to insufficient data, dating errors in some of the proxy records or a breakdown in El Niño–Southern Oscillation's (ENSO's) influence on other regions. However, spectral analysis indicates that each reconstruction portrays ENSO‐like spectral properties. Superposed epoch analysis also shows that each reconstruction shows a generally consistent ‘El Niño‐like’ response to major volcanic events in the following year, while during years T + 4 to T + 7 ‘La Niña‐like’ conditions prevail. These results suggest that each of the series expresses ENSO‐like ‘behaviour’, but this ‘behaviour’ does not appear to be spatially or temporally consistent. This result may reflect published observations that there appear to be distinct ‘types’ of ENSO variability depending on location within the tropical Pacific. Future work must address potential dating issues within some proxies (i.e. sampling of multiple coral heads for one location) as well as assessing the time stability of local climate relationships with central Pacific SSTs. More emphasis is needed on sampling new and extending old coral proxy records from the crucial central and eastern tropical Pacific region. Copyright © 2009 John Wiley & Sons, Ltd. and © Crown Copyright 2009.
GCH1 in early‐onset Parkinson's disease
Authors: Cobb Stephanie A. , Wider Christian , Ross Owen A. , Mata Ignacio F. , Adler Charles H. , Rajput Alex , Rajput Ali H. , Wu Ruey‐Meei , Hauser Robert , Josephs Keith A. , Carr Jonathan , Gwinn Katrina , Heckman Michael G. , Aasly Jan O. , Lynch Timothy , Uitti Ryan J. , Wszolek Zbigniew K. , Kapatos Gregory , Farrer Matthew J. 
Published: September 2009

AbstractMutations in GTP‐cyclohydrolase 1 (GCH1) cause autosomal dominant dopa‐responsive dystonia (DRD), characterized by childhood‐onset foot dystonia that later generalizes. DRD patients frequently present with associated Parkinsonism. Conversely, early‐onset Parkinson's disease (EOPD) patients commonly display dystonia. Herein, we investigated the frequency of GCH1 mutations in a series of 53 familial EOPD patients (21 with dystonia) and screened them for mutations in PRKN, PINK1, and DJ‐1. In addition, we examined a matched EOPD patient–control series for association of common variability at the GCH1 locus and EOPD susceptibility. No GCH1 coding change or copy‐number abnormality was identified in familial EOPD patients. A novel 18‐bp deletion was found in the proximal promoter (two patients, one control), which is expected to knock out two regulatory elements previously shown to regulate GCH1 transcription. No association was found between GCH1 variability and risk of EOPD. Fourteen (26.4%) familial EOPD patients had homozygous or compound heterozygous PRKN mutations. PRKN‐positive patients were 10 years younger than PRKN‐negative patients and had a twofold higher prevalence of dystonia. This study does not support a significant role for genetic variation at the GCH1 locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD. © 2009 Movement Disorder Society
Comparison of weight gain and energy intake after subthalamic versus pallidal stimulation in Parkinson's disease
Authors: Sauleau Paul , Leray Emmanuelle , Rouaud Tiphaine , Drapier Sophie , Drapier Dominique , Blanchard Sophie , Drillet Gwenolla , Péron Julie , Vérin Marc 
Published: September 2009

AbstractTo compare body mass index (BMI) and daily energy intake (DEI) after subthalamic versus pallidal deep brain stimulation (DBS). Weight gain following DBS in Parkinson's disease patients remains largely unexplained and no comparison of subthalamic and pallidal (GPi) stimulation has yet been performed. BMI and DEI, dopaminergic drug administration and motor scores were recorded in 46 patients with PD before STN (n = 32) or GPi (n = 14) DBS and 3 and 6 months after. At M6, BMI had increased by an average of 8.4% in the STN group and 3.2% in the GPi group. BMI increased in 28 STN and 9 GPi patients. This increase was significantly higher in the STN group (P < 0.048) and the difference remained significant after adjustment for reduced dopaminergic medication; 28.6% of GPi patients were overweight at 6 months (14.3% preoperatively) versus 37.5% of STN patients (21.9% preoperatively). Changes in BMI were negatively correlated with changes in dyskinesia in the GPi–DBS group. Food intake did not change in the two groups, either quantitatively or qualitatively. Frequent weight gain, inadequately explained by motor improvement or reduced dopaminergic drug dosage, occurred in subthalamic DBS patients. The difference between groups suggests additional factors in the STN group, such as homeostatic control center involvement. © 2009 Movement Disorder Society
Synthesis of peptide thioesters via an N–S acyl shift reaction under mild acidic conditions on an N‐4,5‐dimethoxy‐2‐mercaptobenzyl auxiliary group
Authors: Nakamura Ken'ichiroh , Kanao Tomoki , Uesugi Tomoya , Hara Toshiaki , Sato Takeshi , Kawakami Toru , Aimoto Saburo 
Published: September 2009

AbstractAn efficient method of peptide thioester synthesis is described. The reaction is based on an N‐4,5‐dimethoxy‐2‐mercaptobenzyl (Dmmb) auxiliary‐assisted N‐S acyl shift reaction after assembling a peptide chain by Fmoc‐solid phase peptide synthesis. The Dmmb‐assisted N‐S acyl shift reaction proceeded efficiently under mildly acidic conditions, and the peptide thioester was obtained by treating the resulting S‐peptide with sodium 2‐mercaptoethanesulfonate. No detectable epimerization of the amino acid residue adjacent to the thioester moiety in the case of Leu was found. The reactions were also amenable to the on‐resin preparation of peptide thioesters. The utility was demonstrated by the synthesis of a 41‐mer peptide thioester, a phosphorylated peptide thioester and a 33‐mer peptide thioester containing a trimethylated lysine residue. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.