bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of uranium depletion on 1α-hydroxylase in kidney of rats
Authors: Minfen Yan  , Gaoren Zhong  , Linfeng Gao  , Xiqiao Xia  , Lihua Wang  , Heping Hu  , Shifang Weng
Published: July 2010

This study was designed to evaluate the effects of depleted uranium (DU) on 1α-hydroxylase in the kidney of rats and to delinerate the mechanism of damage to kidneys and bones by DU. Male Sprague-Dawley rats were surgically implanted with DU fragments at three dose levels (0.1 g, 0.2 g and 0.3 g). After 3, 6 or 12 months, the concentration of 1α,25(OH)2D3 in the kidney was measured by radioimmunoassay. The activity of 1α-hydroxylase was shown by the production of 1α,25(OH)2D3 after incubation. The results showed that the 1α-hydroxylase activity in the kidney was decreased after 3 months (27.2% at the medium dose DU group, p < 0.05; 33.4% at the high dose DU group, p < 0.01). In contrast, at 6 months and 12 months after implantation of DU, the activity of renal 1α-hydroxylase in DU-treated animals was not decreased significantly in comparison with the controls (p > 0.05). On the other hand, the activity of renal 1α-hydroxylase was decreased by 33.1% (p < 0.05) and 34.4% (p < 0.01) in blank control groups at 6 and 12 months, respectively, when compared with the blank control group at 3 months. In conclusion, this study showed that chronic DU exposure could induce renal damages and inhibit the synthesis of biologically active form of vitamin D, which may be the underlying mechanism of bone metabolic disorder caused by renal injury after DU exposure.
Linking Genetics and Mechanics in Structural Protein Materials: A Case Study of an Alport Syndrome Mutation in Tropocollagen
Authors: Srinivasan Maya , Uzel Sebastien G.M. , Gautieri Alfonso , Keten Sinan , Buehler Markus J.
Published: July 2010

Many proteins found in biological systems provide functional properties through the formation of hierarchical materials that feature distinct structures at multiple length-scales, from nano to macro. For example, collagenous tissues are composed of a complex assembly of triple helical collagen molecules and provide the basis for materials such as bone, tendon or connective tissues in organs. The breakdown of these materials due to defects, mutations or large forces can have serious consequences on the functioning of organisms. For example, Alport Syndrome is a severe genetic disease characterized by the breakdown of the glomerular basement membrane (GBM) around blood vessels in the kidney, leading to eventual kidney failure in most patients. It is the second most inherited kidney disease in the United States, and many other symptoms are associated with the disease, including hearing loss and ocular lesions. Here we probe the molecular level mechanisms of this disease, utilizing a bottom-up computational materiomics approach focused on the mutation associated with the most severe form of Alport Syndrome. Since the GBM is under constant mechanical loading due to blood flow, changes in mechanical properties due to amino acid mutations may be critical in the symptomatic GBM breakdown seen in Alport Syndrome patients. The purpose of this article is to review recent molecular dynamics simulations of structural and mechanical aspects of this disease at the single-molecule level (Srinivasan et al., Journal Of Structural Biology, 168(3), 503—510 (2010)), and to provide a general outlook into opportunities and challenges in the field of using molecular mechanics to improve our understanding of disease mechanisms (Buehler and Yung, Nature Materials, 8(3), 175—188 (2009)). We review a series of full-atomistic simulations in explicit solvent, which reveal the effects of single-residue glycine substitution mutations in a short segment of a collagen type IV tropocollagen molecule. Major changes are observed at the single-molecule level of the mutated sequence, including a bent shape of the structures after equilibration, with the kink located at the mutation site and a significant alteration of the molecule’s stress—strain response and stiffness. We also provide a general discussion on computational approaches to study the link between genetics and functional mechanical properties of tissues.
The Multiple Sclerosis Severity Score: associations with MC1R single nucleotide polymorphisms and host response to ultraviolet radiation
Authors: Strange Richard C , Ramachandran Sudarshan , Zeegers Maurice P , Emes Richard D , Abraham Roby , Raveendran Vythilingam , Boggild Mike , Gilford Janice , Hawkins Clive P
Published: July 2010

Background: Multiple sclerosis outcome may be influenced by ultraviolet radiation and vitamin D synthesis, suggesting skin type and genes determining this phenotype are candidates for disability. However, though associations between melanocortin 1 receptor (MC1R) single nucleotide polymorphisms and disability are reported, some data are incompatible with their expected influence on skin type.

Objective: Determine which MC1R single nucleotide polymorphisms affect disability and establish if ultraviolet radiation modifies such associations.

Methods: We studied using linear regression in 525 cases, associations of the Multiple Sclerosis Severity Score (MSSS) with skin type, gender, ultraviolet radiation exposure and six MC1R single nucleotide polymorphisms (rs1805005, rs1805006, rs2228479, rs1805007, rs1805008, rs1805009).

Results: CG294 with GG294 genotypes (rs1805009) (coefficient = —1.44, 95% CI —2.30, —0.59, mean MSSS ± SD = 4.33 ± 2.87) and AC84 (rs1805006) (coefficient = 1.62, 95% CI 0.17, 3.06, mean MSSS = 7.62 ± 2.43) were associated with MSSS. Associations with Asp294His were found in those with skin types 1/2 and 3/4, and cases stratified by ultraviolet radiation exposure. However, they were seen only in cases with a history of childhood sunburn and not in those without sunburn. We found no significant associations between exposure parameters and MSSS.

Conclusions: Multiple Sclerosis outcome is influenced by interactions between host response to ultraviolet radiation and MC1R single nucleotide polymorphisms. The influence of the single nucleotide polymorphisms appears distinct from their association with skin type.
Preclinical studies of methylthioadenosine for the treatment of multiple sclerosis
Authors: Moreno B. , Fernandez-Diez B. , Di Penta A. , Villoslada P.
Published: July 2010

Background: Methylthioadenosine (MTA) is a natural metabolite with immunomodulatory properties. MTA improves the clinical course and pathology of the animal model of multiple sclerosis, even when therapy is started after disease onset. Objective: Our aim was to compare the efficacy of MTA in ameliorating experimental autoimmune encephalomyelitis (EAE) compared with first line approved therapies, to develop an oral formulation of MTA and to assess its pharmacokinetic profile.

Methods: EAE was induced in C57BL/6 mice by immunization with MOG35-55 peptide in Freund’s Adjuvant. Animals were treated with MTA, interferon-beta or Glatiramer acetate starting the day of immunization and the clinical score was collected blind. Pharmacokinetic studies were performed in Sprague Dawley rats by administering MTA by intraperitoneal injection and orally, and collecting blood at different intervals. MTA levels were measured by high-performance liquid chromatography.

Results: We found that MTA ameliorated EAE in a dose—response manner. Moreover, the highest dose of MTA (60 mg/kg) was more efficacious than mouse interferon-beta or Glatiramer acetate. We developed a salt of MTA for oral administration, with similar dose—response effect in the EAE model. Combination therapy assays between MTA and interferon-beta or Glatiramer acetate were more effective than the individual therapies. Finally, oral MTA half-life was 20 min, with a Cmax of 80 mg/L and without signs of obvious toxicity (animal death, behavioural changes, liver enzymes). Conclusions: In the EAE model MTA is more efficacious than first line therapies for multiple sclerosis, with a dose— response effect and higher efficacy when combined with interferon-beta or Glatiramer acetate. Oral MTA was also effective in the animal model of multiple sclerosis.
Modifications to the McDonald MRI dissemination in space criteria for use in Asians with classic multiple sclerosis: the Taiwanese experience
Authors: Chen Shao-Yuan , Lo Chung-Ping , Hsu Wen-Lin , Kao Hung-Wen , Hsueh Chun-Jen , Lin Wei-Chen , Liu Chia-Chen , Wang Wei-Yu , Hsu Chia-Chun
Published: July 2010

Background: The McDonald MRI dissemination in space criteria have been found to be less sensitive when applied to Asians with classic multiple sclerosis. The Asian neurological community thus proposed modifications to the criteria with reduction of minimal number of T2 lesions from nine to four, and removal of restriction on spinal cord lesion length and morphology for use in Asians.

Objective: The study is to examine the accuracy of modified MRI dissemination in space criteria for prediction of conversion from clinically isolated syndrome to definite multiple sclerosis according to patients’ baseline MRI.

Methods: From 2001 to 2007, we recruited 67 patients with clinically isolated syndrome. They had been followed-up until development of definite multiple sclerosis or remaining as clinically isolated syndrome for more than 2 years. The non-converters were taken as negative cases. The 67 patients’ baseline MRIs were evaluated by two radiologists and determined as either fulfilling or not fulfilling McDonald and modified MRI criteria for dissemination in space.

Results: Thirty-two patients converted to definite multiple sclerosis and 35 did not. The modified criteria are slightly more sensitive (53.1% vs. 50.0%) and accurate (77.6% vs. 76.1%) as compared with McDonald criteria. However, further reduction of the cutoff of abnormal MRI criteria from three of four to two of four criteria yields best sensitivity (71.9%) and accuracy (83.6%).

Conclusions: Modifications to the McDonald MRI dissemination in space criteria (by using fewer T2 lesions, removal of the restriction on the spinal cord lesion and reduction of the cutoff of MRI criteria) are more appropriate for use in the Taiwanese population for the diagnosis of classic multiple sclerosis.
Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in relapsing—remitting multiple sclerosis
Authors: Calabrese Massimiliano , Rinaldi Francesca , Grossi Paola , Mattisi Irene , Bernardi Valentina , Favaretto Alice , Perini Paola , Gallo Paolo
Published: July 2010

Background: Fatigue is one of the most frequent symptoms suffered by patients affected by multiple sclerosis. The patho-physiological basis of multiple sclerosis-related fatigue remains to be elucidated.

Objective: Our aim was to investigate whether a particular pattern of deep and/or cortical grey matter atrophy is associated with fatigue in patients with multiple sclerosis.

Methods: A total of 152 patients with relapsing—remitting multiple sclerosis were evaluated with the Expanded Disability Status Scale, the Fatigue Severity Status Scale (FSS), the Modified Fatigue Impact Scale and the Beck Depression Inventory. The thalamic and basal ganglia volume and the regional cortical thickness were analysed by means of FreeSurfer.

Results: Based on Fatigue Severity Status Scale score, patients were divided into fatigued (FSS ≥ 4, 71 patients, 46.6%) and non-fatigued (FSS < 4, 81 patients, 53.4%). A significant atrophy of striatum, thalamus, superior frontal gyrus and inferior parietal gyrus was observed in fatigued patients compared with non-fatigued patients. The cognitive domain of Modified Fatigue Impact Scale significantly correlated with the volume of the striatum and with the cortical thickness of the posterior parietal cortex and middle frontal gyrus (R = 0.51—0.61), while the physical domain of Modified Fatigue Impact Scale significantly correlated with striatum volume and superior frontal gyrus cortical thickness (R = 0.50—0.54). Conclusions: The regional analysis of deep and cortical grey matter atrophy suggests an association between the neurodegenerative process taking place in the striatum—thalamus—frontal cortex pathway and the development of fatigue in relapsing—remitting multiple sclerosis. The inclusion of the posterior parietal cortex as one of the best predictors of the Modified Fatigue Impact Scale cognitive domain suggests the major role of the posterior attentional system in determining cognitive fatigue in relapsing—remitting multiple sclerosis.
Diagnosing multiple sclerosis at a later age: more than just progressive myelopathy
Authors: Bermel Robert A , Rae-Grant Alexander D , Fox Robert J
Published: July 2010

Background: Multiple sclerosis (MS) is usually considered a ‘young persons’ disease’, typically presenting between the ages of 20 and 40. In this study we review our experience with patients diagnosed at age 60 or over, with particular emphasis on patients who continue to have evidence of active inflammation despite a later onset.

Methods: We reviewed all cases of MS diagnosed at or over age 60 in our center over a 5-year period. We identified 111 patients and recorded their clinical and imaging characteristics using prespecified variables. Analyses were performed to describe their interval to diagnosis, clinical syndromes, imaging and laboratory characteristics.

Results: At the time of diagnosis, 8% of patients had a clinically isolated syndrome, 33% were in the relapsing—remitting stage, while 23% had a secondary progressive course, and 32% were primary progressive. Eighty-eight percent of patients had a brain MRI judged ‘typical for MS’, and 32% of all patients receiving gadolinium had enhanced lesions. Forty-six percent of patients with relapsing—remitting MS or clinically isolated syndrome exhibited gadolinium enhancement. Myelitis was the most common initial clinical syndrome, and progressive myelopathy was a common but not exclusive clinical syndrome at the time of diagnosis.

Conclusions: A relapsing pattern of MS is not uncommon, even in patients diagnosed over the age of 60. Active inflammation (clinical relapses and gadolinium enhancement) occurs in a significant number of patients with MS with later diagnosis. These observations have implications for evaluation and treatment of patients with MS presenting at an older age.
A case of cerebral aquaporinopathy
Authors: Tanaka A. , Yoshida T. , Yamada T. , Isayama R. , Fujiwara Y. , Shiga K. , Yamada K. , Tanaka K. , Nakagawa M.
Published: July 2010

A 35-year-old woman was hospitalized due to impaired consciousness. Magnetic resonance imaging (MRI) revealed multiple parenchymal lesions in supra and infratentorial brain regions, which were considered responsible for her declining consciousness level. She was treated with intravenous methylprednisolone. Neurological symptoms improved and she was discharged. She was readmitted 14 months later due to intractable hiccups. A follow-up brain MRI revealed an abnormal signal near the area postrema in the dorsal medulla. Serum aquaporin-4 antibody levels were positive, but there were no visual manifestations or myelitis. Spinal MRI was negative for longitudinally extended transverse myelitis throughout the clinical course.
Assessing expressed emotion in mothers of children with autism
Authors: Benson Paul R. , Daley Dave , Karlof Kristie L. , Robison Dorothy
Published: July 2010

Background: Expressed emotion (EE) is a measure of family emotional climate found to be predictive of symptom levels in a range of psychiatric, medical, and developmental disorders, including autism. Method: Employing data from 104 mothers of children with autism, this study examines the Autism-Specific Five Minute Speech Sample (AFMSS), a modified EE coding system based on the widely used Five Minute Speech Sample (Magana et al., 1986). Findings: With the exception of one EE component, emotional over-involvement, the revised coding system demonstrated adequate internal consistency and good to excellent inter-rater and code-recode reliability. It also demonstrated acceptable validity, based on its significant correlations with factors linked to EE in previous research. Regression analyses also indicated AFMSS-EE to be a significant predictor of child social competence, but not child problem behaviors. Discussion: While further testing is required, the AFMSS appears to be a useful method of assessing EE within the context of parenting children with autism and related disorders.
Influence of heating source position and dilution rate in achieving overmatched dissimilar welded joints
Authors: Iordachescu M. , Iordachescu D. , Scutelnicu E. , Ruiz-Hervias J. , Valiente A. , Caballero L.
Published: July 2010

The investigation addresses the overall performance of black and white joints (BWJ) of low carbon steel (LCS) and stainless steel thin sheets achieved by laser hybrid welding. Assuming that the structural integrity is directly influenced by the processing temperature, a thermal simulation of BWJ of thin sheets was developed. Afterwards, the base metals apportionment at joint formation, namely their distinct dilution rate, was originally estimated from the top surface temperature variation. Defect-free laser hybrid dissimilar welds were experimentally obtained using the selected filler metal and the energetic input from the process simulation, even for a critical analysed case of heat source displacement from the weld gap centreline towards LCS. Detailed macro and microstructural examination of the BWJ and related microhardness analysis results are presented. The tensile tests results indicate that in the case of transversally loaded BWJ, the positive difference in yield between the weld metal and the base materials protects the weld metal from being plastically deformed; the flat transverse tensile specimens loading up to failure reveals large strains in LCS, far away from the weld.
Effect of low transformation temperature weld filler metal on welding residual stress
Authors: Murakawa H. , Béreš M. , Davies C. M. , Rashed S. , Vega A. , Tsunori M. , Nikbin K. M. , Dye D.
Published: July 2010

The effect of weld filler metal austenite to acicular ferrite transformation temperature on the residual stresses that arise during the gas metal arc welding of a low carbon steel has been examined using a finite element model. It was found that the stress levels in the weld can be tailored by the appropriate selection of the filler metal and compressive, near zero or tensile residual stresses produced. Reasonable agreement was obtained between the model and the stresses measured using neutron diffraction both in welds using conventional and low transformation temperature filler metal.
Method for welding highly crack susceptible magnesium alloy ZK60
Authors: Yu Z. H. , Yan H. G. , Chen S. J. , Chen J. H. , Zeng P. L.
Published: July 2010

The highly crack susceptible magnesium alloy ZK60 plates of 2 mm thickness were successfully welded by laser beam welding (LBW) with filler strip, which has the advantages of low heat input and capability of adjusting the compositions of weld metal to a less susceptible level. The effects of the compositions of filler strips on the microstructures and mechanical properties of the joints were investigated. Compared with autogenous LBW, LBW with filler strip can produce a narrower joint and avoid the cracks and pits, which severely worsen mechanical properties of the joints. When the filler strip of ZK40 alloy is employed, the grains in fusion zone can be refined, and a high quality joint, with the ultimate tensile strength of 322 MPa up to 90·7% of the base metal, is obtained.
Friction stir welding of dissimilar A319 and A356 aluminium cast alloys
Authors: Hassan A. S. , Mahmoud T. S. , Mahmoud F. H. , Khalifa T. A.
Published: July 2010

In the present investigation, the microstructure and mechanical characteristics of dissimilar A319 and A356 cast Al alloys plates joined by friction stir welding (FSW) were evaluated. The effect of tool rotational and welding speeds as well as the post-weld heat treatment (PWHT) on such properties was investigated. Post-weld heat treatment was carried out at a solutionising temperature of 540°C for 12 h followed by aging at 155°C for 6 h. For the as welded specimens, the welded zone (WZ) exhibited higher hardness values when compared with the A319 and A356 parent alloys. The peak hardness at the WZ was found to increase by increasing the tool rotational speed and/or reducing the welding speed. In contrast, the post-weld heat treated (PWHTed) specimens exhibited lower hardness values at the WZ than the parent alloys. For PWHTed specimens, the peak hardness at the WZ was found to decrease by increasing the tool rotational speed and/or reducing the welding speed. Tensile tests results demonstrate that, for the as welded specimens, the tensile fracture took place on A356 side where the hardness was minimal. While for PWHTed specimens, the fracture took place at the WZ. Increasing the tool rotational speed reducing both tensile and yield strengths, but increases the ductility of the joint.
Modulated Nd : YAG laser welding of Ti–6Al–4V
Authors: Blackburn J. E. , Allen C. M. , Hilton P. A. , Li L. , Hoque M. I. , Khan A. H.
Published: July 2010

Modulating the output of Nd : YAG laser sources has been evaluated as a technique for producing high quality welds in titanium alloys. Welds with high internal quality were produced when a square wave form was used with a modulation frequency ≥125 Hz and a duty cycle of 50%. Undercut present in the weld profile can be reduced if the correct combination of modulation amplitude and laser beam focal plane position are used. High speed observation and subsequent Fourier analysis of the vapour plume and keyhole behaviour have shown that they both exhibit the same periodic tendencies. With the correct parameters, an oscillating wave can be set up in the weld pool, which appears to manipulate the vapour plume behaviour and hence reduce porosity formation.
On formability of tailor laser welded blanks of DP/TRIP steel sheets
Authors: Ahmed E. , Reisgen U. , Schleser M. , Mokrov O.
Published: July 2010

This paper aims to evaluate the formability of tailor welded blanks of dual phase (DP600)/transformation induced plasticity (TRIP700) steel sheets. In this work, bead on plate butt joints of 2·5 mm DP600 and 1·2 mm TRIP700 steel sheets were performed using CO2 laser beam welding. Microhardness measurements and transverse tensile testing were carried out to characterise the welds. The formability of base metals and welds were investigated by standard Erichsen test. In a perpendicular tensile test to the weld line, all specimens were fractured at the TRIP base metal, and the strengths were somewhat higher than those of base metal. There was a significant reduction in formability caused by welding of the DP600/TRIP700 steel sheets, and the formability increased with increasing welding speed.
Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells
Authors: Cocco Claudia , Canale Sara , Frasson Chiara , Di Carlo Emma , Ognio Emanuela , Ribatti Domenico , Prigione Ignazia , Basso Giuseppe , Airoldi Irma
Published: July 2010

Interleukin (IL)–23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric B-acute lymphoblastic leukemia (B-ALL) cells and to unravel the molecular mechanisms involved. Here, we show, for the first time, that IL-23R is up-regulated in primary B-ALL cells, compared with normal early B lymphocytes, and that IL-23 dampens directly tumor growth in vitro and in vivo through the inhibition of tumor cell proliferation and induction of apoptosis. The latter finding is related to IL-23–induced up-regulation of miR15a expression and the consequent down-regulation of BCL-2 protein expression in pediatric B-ALL cells. This study demonstrates that IL-23 possesses antileukemic activity and unravels the underlying mechanisms. Thus, IL-23 may be a candidate novel drug for the treatment of B-ALL patients unresponsive to current therapeutic standards.
Integration and visualization of systems biology data in context of the genome
Authors: Bare J Christopher , Koide Tie , Reiss David J , Tenenbaum Dan , Baliga Nitin S
Published: July 2010

Background

High-density tiling arrays and new sequencing technologies are generating rapidly increasing volumes of transcriptome and protein-DNA interaction data. Visualization and exploration of this data is critical to understanding the regulatory logic encoded in the genome by which the cell dynamically affects its physiology and interacts with its environment.

Results

The Gaggle Genome Browser is a cross-platform desktop program for interactively visualizing high-throughput data in the context of the genome. Important features include dynamic panning and zooming, keyword search and open interoperability through the Gaggle framework. Users may bookmark locations on the genome with descriptive annotations and share these bookmarks with other users. The program handles large sets of user-generated data using an in-process database and leverages the facilities of SQL and the R environment for importing and manipulating data.

A key aspect of the Gaggle Genome Browser is interoperability. By connecting to the Gaggle framework, the genome browser joins a suite of interconnected bioinformatics tools for analysis and visualization with connectivity to major public repositories of sequences, interactions and pathways. To this flexible environment for exploring and combining data, the Gaggle Genome Browser adds the ability to visualize diverse types of data in relation to its coordinates on the genome.

Conclusions

Genomic coordinates function as a common key by which disparate biological data types can be related to one another. In the Gaggle Genome Browser, heterogeneous data are joined by their location on the genome to create information-rich visualizations yielding insight into genome organization, transcription and its regulation and, ultimately, a better understanding of the mechanisms that enable the cell to dynamically respond to its environment.
GU81, a VEGFR2 antagonist peptoid, enhances the anti-tumor activity of doxorubicin in the murine MMTV-PyMT transgenic model of breast cancer
Authors: Lynn Kristi D , Udugamasooriya D Gomika , Roland Christina L , Castrillon Diego H , Kodadek Thomas J , Brekken Rolf A
Published: July 2010

Background

Vascular endothelial growth factor (VEGF) is a primary stimulant of angiogenesis under physiological and pathological conditions. Anti-VEGF therapy is a clinically proven strategy for the treatment of a variety of cancers including colon, breast, lung, and renal cell carcinoma. Since VEGFR2 is the dominant angiogenic signaling receptor, it has become an important target in the development of novel anti-angiogenic therapies. We have reported previously the development of an antagonistic VEGFR2 peptoid (GU40C4) that has promising anti-angiogenic activity in vitro and in vivo.

Methods

In the current study, we utilize a derivative of GU40C4, termed GU81 in therapy studies. GU81 was tested alone or in combination with doxorubicin for in vivo efficacy in the MMTV-PyMT transgenic model of breast cancer.

Results

The derivative GU81 has increased in vitro efficacy compared to GU40C4. Single agent therapy (doxorubicin or GU81 alone) had no effect on tumor weight, histology, tumor fat content, or tumor growth index. However, GU81 is able to significantly to reduce total vascular area as a single agent. GU81 used in combination with doxorubicin significantly reduced tumor weight and growth index compared to all other treatment groups. Furthermore, treatment with combination therapy significantly arrested tumor progression at the premalignant stage, resulting in increased tumor fat content. Interestingly, treatment with GU81 alone increased tumor-VEGF levels and macrophage infiltration, an effect that was abrogated when used in combination with doxorubicin.

Conclusion

This study demonstrates the VEGFR2 antagonist peptoid, GU81, enhances the anti-tumor activity of doxorubicin in spontaneous murine MMTV-PyMT breast tumors.
A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group
Authors: Lang Reinhold , Baumann Petra , Jauch Karl-Walter , Schmoor Claudia , Weis Christine , Odermatt Erich , Knaebel Hanns-Peter
Published: July 2010

Background

Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed.

Methods/Design

This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part® Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10) days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10) days and 3 months (±14 days) after surgery.

Discussion

This trial aims to assess, whether the intra-peritoneal application of A-Part® Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls.

Trial registration

NCT00646412
Simvastatin attenuates ventilator-induced lung injury in mice
Authors: Müller Holger C , Hellwig Katharina , Rosseau Simone , Tschernig Thomas , Schmiedl Andreas , Gutbier Birgitt , Schmeck Bernd , Hippenstiel Stefan , Peters Harm , Morawietz Lars , Suttorp Norbert , Witzenrath Martin
Published: July 2010

Introduction

Mechanical ventilation (MV) is a life saving intervention in acute respiratory failure without alternative. However, particularly in pre-injured lungs, even protective ventilation strategies may evoke ventilator-induced lung injury (VILI), which is characterized by pulmonary inflammation and vascular leakage. Adjuvant pharmacologic strategies in addition to lung protective ventilation to attenuate VILI are lacking. Simvastatin exhibited anti-inflammatory and endothelial barrier stabilizing properties in vitro and in vivo.

Methods

Mice were ventilated (12 ml/kg; six hours) and subjected to simvastatin (20 mg/kg) or sham treatment. Pulmonary microvascular leakage, oxygenation, pulmonary and systemic neutrophil and monocyte counts and cytokine release in lung and blood plasma were assessed. Further, lung tissue was analyzed by electron microscopy.

Results

Mechanical ventilation induced VILI, displayed by increased pulmonary microvascular leakage and endothelial injury, pulmonary recruitment of neutrophils and Gr-1high monocytes, and by liberation of inflammatory cytokines in the lungs. Further, VILI associated systemic inflammation characterized by blood leukocytosis and elevated plasma cytokines was observed. Simvastatin treatment limited pulmonary endothelial injury, attenuated pulmonary hyperpermeability, prevented the recruitment of leukocytes to the lung, reduced pulmonary cytokine levels and improved oxygenation in mechanically ventilated mice.

Conclusions

High-dose simvastatin attenuated VILI in mice by reducing MV-induced pulmonary inflammation and hyperpermeability.
The Disulfide Relay of the Intermembrane Space of Mitochondria: An Oxygen‐Sensing System?
Authors: Bihlmaier Karl , Mesecke Nikola , Kloeppel Christine , Herrmann Johannes M.
Published: July 2010

The intermembrane space of mitochondria contains many proteins that lack classical mitochondrial targeting sequences. Instead, these proteins often show characteristic patterns of cysteine residues that are critical for their accumulation in the organelle. Import of these proteins is catalyzed by two essential components, Mia40 and Erv1. Mia40 is a protein in the intermembrane space that directly binds newly imported proteins via disulfide bonds. By reorganization of these bonds, intramolecular disulfide bonds are formed in the imported proteins, which are thereby released from Mia40 into the intermembrane space. Because folded proteins are unable to traverse the import pore of the outer membrane, this leads to a permanent location of these proteins within the mitochondria. During this reaction, Mia40 becomes reduced and needs to be re‐oxidized to regain its activity. Oxidation of Mia40 is carried out by Erv1, a conserved flavine adenine dinucleotide (FAD)‐binding sulfhydryl oxidase. Erv1 directly interacts with Mia40 and shuttles electrons from reduced Mia40 to oxidized cytochrome c, from whence they flow through cytochrome oxidase to molecular oxygen. The connection of the disulfide relay with the respiratory chain not only significantly increases the efficiency of the oxidase activity, but also prevents the formation of potentially deleterious hydrogen peroxide. The oxidative activity of Erv1 strongly depends on the oxygen concentration in mitochondria. Erv1, therefore, may function as a molecular switch that adapts mitochondrial activities to the oxygen levels in the cell.
The mechanical power output of the pectoralis muscle of cockatiel (Nymphicus hollandicus): thein vivomuscle length trajectory and activity patterns and their implications for power modulation
Authors: Morris Charlotte R. , Askew Graham N.
Published: July 2010

In order to meet the varying demands of flight, pectoralis muscle power output must be modulated. In birds with pectoralis muscles with a homogeneous fibre type composition, power output can be modulated at the level of the motor unit (via changes in muscle length trajectory and the pattern of activation), at the level of the muscle (via changes in the number of motor units recruited), and at the level of the whole animal (through the use of intermittent flight). Pectoralis muscle length trajectory and activity patterns were measured in vivo in the cockatiel (Nymphicus hollandicus) at a range of flight speeds (0–16 m s−1) using sonomicrometry and electromyography. The work loop technique was used to measure the mechanical power output of a bundle of fascicles isolated from the pectoralis muscle during simulated in vivo length change and activity patterns. The mechanical power–speed relationship was U-shaped, with a 2.97-fold variation in power output (40–120 W kg−1). In this species, modulation of neuromuscular activation is the primary strategy utilised to modulate pectoralis muscle power output. Maximum in vivo power output was 22% of the maximum isotonic power output (533 W kg−1) and was generated at a lower relative shortening velocity (0.28Vmax) than the maximum power output during isotonic contractions (0.34Vmax). It seems probable that the large pectoralis muscle strains result in a shift in the optimal relative shortening velocity in comparison with the optimum during isotonic contractions as a result of length–force effects.
A high-precision reconstructing technique for a high-frequency acoustic field based on the angular spectrum method
Authors: Shao Y , Mei D , Fan Z , Yang K
Published: July 2010

To apply ultrasonic radiation force in precise manipulation for micro-components, a reconstruction technique for low-frequency sound field based on angular spectrum method (ASM) was adopted in the reconstruction for high-frequency sound field, and a high-precision reconstructing technique for high-frequency sound field was developed. First, the principle of reconstructing the sound field by ASM and four key factors on reconstruction precision were analysed. Second, the marginal Gibbs phenomenon and aperture replication effect were decreased by optimizing of the sampling interval and holographical aperture, and the signal-to-noise ratio (SNR) was increased by using the tapered filter to pretreat the signal data in wave number space. Then, the ill-posedness in reverse problem was eliminated by using a new kind of k-space filter to refine the transfer function. Finally, the reconstruction experiment of 1.75 MHz ultrasonic field was conducted by using the three-dimensional precise scanning system and needle-type hydrophone, and the experimental results validate the feasibility and efficiency of the method proposed in this study.
An exact solution for free vibration of thin functionally graded rectangular plates
Authors: Baferani A Hasani , Saidi A R , Jomehzadeh E
Published: July 2010

The aim of this article is to find an exact analytical solution for free vibration characteristics of thin functionally graded rectangular plates with different boundary conditions. The governing equations of motion are obtained based on the classical plate theory. Using an analytical method, three partial differential equations of motion are reformulated into two new decoupled equations. Based on the Navier solution, a closed-form solution is presented for natural frequencies of functionally graded simply supported rectangular plates. Then, considering Levy-type solution, natural frequencies of functionally graded plates are presented for various boundary conditions. Three mode shapes of a functionally graded rectangular plate are also presented for different boundary conditions. In addition, the effects of aspect ratio, thickness—length ratio, power law index, and boundary conditions on the vibration characteristics of functionally graded rectangular plates are discussed in details. Finally, it has been shown that the effects of in-plane displacements on natural frequencies of functionally graded plates under different boundary conditions have been studied.
Optimum design of rolling element bearings using a genetic algorithm—differential evolution (GA—DE) hybrid algorithm
Authors: Lin W Y
Published: July 2010

Binary-code genetic algorithms (BGA) have been used to obtain the optimum design for deep groove ball bearings, based on maximum fatigue life as an objective function. The problem has ten design variables and 20 constraint conditions. This method can find better basic dynamic loads rating than those listed in standard catalogues. However, the BGA algorithm requires a tremendous number of evaluations of the objective function per case to achieve convergence (e.g. about 5 200 000 for a representative case). To overcome this difficulty, a hybrid evolutionary algorithm by combining real-valued genetic algorithm (GA) with differential evolution (DE) is used together with the proper handling of constraints for this optimum design task. Findings show that the GA—DE algorithm can successfully find the better dynamic loads rating, about 1.3—11.1 per cent higher than those obtained using the traditional BGA. Moreover, the mean number of evaluations of the objective function required to achieve convergence is about 3011, using the GA—DE algorithm, as opposed to about 5 200 000 for a representative case using the BGA. Comparison shows the GA—DE algorithm to be much more effective and efficient than the BGA.
Properties of Composite Specimens of Old and New Bone Cement
Authors: Acharya A , Timperley A J , Lee A J C
Published: July 2010

The most common cause of failure of a total hip replacement is aseptic loosening of an implant. In a number of cases, the cement—bone interface of at least one component is not compromised. In cases of aseptic cup loosening, removal of a well-fixed femoral stem may be undertaken to facilitate exposure of the acetabulum for cup revision, and the surgeon may choose to leave the functional cement—bone interfaces in the femur undisturbed. After cup revision, new cement is pressurized within the old cement mantle and a stem is cemented into this ‘old—new cement’ composite. Retaining the old cement mantle is an attractive option as it reduces the duration of surgery, minimizes bleeding, and preserves the bone stock. Excellent results have been shown with this technique of ‘in-cement femoral revision’ using a double-tapered polished stem. While considerable literature is available on the short- and long-term properties of PMMA bone cement, very little is known about the mechanical properties of old—new composite cement specimens where the old cement is more than a few days old. This paper tests the properties of such old—new composite specimens where the ‘old’ cement is aged between 3.3 and 17.7 years, better reflecting clinical situations.
Validation of a Morphometric Reconstruction Technique Applied to a Juvenile Pelvis
Authors: Watson P J , O'Higgins P , Fagan M J , Dobson C A
Published: July 2010

Three-dimensional reconstructions of bone geometry from microCT (computed tomography) data are frequently used in biomechanical and finite element analyses. Digitization of bone models is usually a simple process for specimens with a complete geometry, but in instances of damage or disarticulation it can be very challenging. Subsequent to digitization, further imaging techniques are often required to estimate the geometry of missing bone or connecting cartilage. This paper presents an innovative approach to the reconstruction of incomplete scan data, to reproduce proper anatomical arrangements of bones, including absent connecting cartilaginous elements. Utilizing geometric morphometric tools, the reconstruction technique is validated through comparison of a reconstructed 9 year old pelvis, to the original CT data. A principal component analysis and an overlay of the two pelves provide a measure of the accuracy of the reconstructed model. Future work aims to investigate the biomechanical effects of any minor positional error on the bone's predicted structural properties through the use of finite element analysis.
The Role of Multilateral Institutions in International Trade Cooperation
Authors: Maggi Giovanni
Published: July 2010

The World Trade Organization (WTO) lacks the power to directly enforce agreements. It is therefore important to understand what role the WTO can play to facilitate international cooperation, and whether a multilateral institution can offer distinct advantages over a web of bilateral agreements. This paper examines two potential benefits of a multilateral trade institution: first, verifying violations of the agreements and informing third parties, thus facilitating multilateral reputation mechanisms; second, promoting multilateral trade negotiations rather than a web of bilateral negotiations. The model suggests that a multilateral approach is particularly important when there are strong imbalances in bilateral trading relationships. (JEL F13)
Technological Revolutions
Authors: Caselli Francesco
Published: July 2010

In skill-biased (de-skilling) technological revolutions learning investments required by new machines are greater (smaller) than those required by preexisting machines. Skill-biased (de-skilling) revolutions trigger reallocations of capital from slow- (fast- ) to fast- (slow- ) learning workers, thereby reducing the relative and absolute wages of the former. The model of skill-biased (de-skilling) revolutions provides insight into developments since the mid-1970's (in the 1910's). The empirical work documents a large increase in the interindustry dispersion of capital-labor ratios since 1975. Changes in industry capital intensity are related to the skill composition of the labor force. (JEL E23 J31 O33)
Competing for Endorsements
Authors: Grossman Gene M , Helpman Elhanan
Published: July 2010

Endorsements are a simple language for communication between interest-group leaders and group members. The members, who share policy concerns, may not perfectly understand where their interests lie on certain issues. If their leaders cannot fully explain the issues, they can convey some information by endorsing a candidate or party. When interest groups endorse legislative contenders, the candidates may compete for backing. Policies may favor special interests at the expense of the general public. We examine the conditions under which parties compete for endorsements, the extent to which policy outcomes are skewed, and the normative properties of the political equilibria. (JEL D72)
What's in a Name? Reputation as a Tradeable Asset
Authors: Tadelis Steven
Published: July 2010

I develop a model in which a firm's only asset is its name, which summarizes its reputation, and study the forces that cause names to be valuable, tradeable assets. An adverse selection model in which shifts of ownership are not observable guarantees an active market for names with either finite or infinite horizons. No equilibrium exists in which only good types buy good names. The reputational dynamics that emerge from the model are more realistic than those in standard game-theoretic reputation models, and suggest that adverse selection plays a crucial role in understanding firm reputation. (JEL C70, D80, L14)
Gaming Against Managers in Incentive Systems: Experimental Results with Chinese Students and Chinese Managers
Authors: Cooper David J , Kagel John H , Lo Wei , Gu Qing Liang
Published: July 2010

We examine strategic interactions between firms and planners in China, comparing behavior between: (i) students and managers with field experience with this situation, (ii) standard versus increased monetary incentives, and (iii) sessions conducted “in context,” making explicit reference to interactions between planners and managers, and those without any such references. The dynamics of play are similar across treatments with play only gradually, and incompletely, converging on a pooling equilibrium. A fivefold increase in incentives significantly increases initial levels of strategic play. Games played in context generated greater levels of strategic play for managers, with minimal impact on students. (JEL D23, D8, C92)
Emergence of Money as a Medium of Exchange: An Experimental Study
Authors: Duffy John , Ochs Jack
Published: July 2010

This paper reports findings from an experiment that implements a search-theoretic model of money as a medium of exchange. The question examined is whether subjects learn to adopt the same commodities as media of exchange that the model predicts will be used in equilibrium. We report that subjects have a strong tendency to play “fundamental” rather than “speculative” strategies even in environments where speculative strategies yield higher payoffs. We examine some possible motivations for subjects' behavior and conclude that subjects are mainly motivated by past payoff experience as opposed to the marketability considerations that the theory emphasizes. (JEL D83, E40)
Household Production and the Excess Sensitivity of Consumption to Current Income
Authors: Baxter Marianne , Jermann Urban J
Published: July 2010

Empirical research on the permanent-income hypothesis (PIH) has found that consumption growth is excessively sensitive to predictable changes in income. This finding is interpreted as strong evidence against the PIH. We propose an explanation for apparent excess sensitivity that is based on a quantitative equilibrium model of household production in which permanent-income consumers respond to shifts in sectoral wages and prices by substituting work effort and consumption across home and market sectors. Although the PIH is true, this mechanism generates apparent excess sensitivity because market consumption responds to predictable income growth. (JEL D13, E10, E21).