bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor suppressor gene RBM5 delivered by attenuated Salmonella inhibits lung adenocarcinoma through diverse apoptotic signaling pathways
Authors: Shao Chen , Yang Baoxue , Zhao Lijing , Wang Song , Zhang Jie , Wang Ke
Published: May 2013

Background

RBM5 (RNA-binding motif protein 5, also named H37/LUCA-15) gene from chromosome 3p21.3 has been demonstrated to be a tumor suppressor. Current researches in vitro confirm that RBM5 can suppress the growth of lung adenocarcinoma cells by inducing apoptosis. There is still no effective model in vivo, however, that thoroughly investigates the effect and molecular mechanism of RBM5 on lung adenocarcinoma.

Method

We established the transplanted tumor model on BALB/c nude mice using the A549 cell line. The mice were treated with the recombinant plasmids carried by attenuated Salmonella to induce the overexpression of RBM5 in tumor tissues. RBM5 overexpression was confirmed by immunohistochemistry staining. H&E staining was performed to observe the histological performance on plasmids-treated A549 xenografts. Apoptosis was assessed by TUNEL staining with a TUNEL detection kit. Apoptosis-regulated genes were detected by Western blot.

Results

We successful established the lung adenocarcinoma animal model in vivo. The growth of tumor xenografts was significantly retarded on the mice treated with pcDNA3.1-RBM5 carried by attenuated Salmonella compared to that on mice treated with pcDNA3.1. Overexpression of RBM5 enhanced the apoptosis in tumor xenografts. Furthermore, the expression of Bcl-2 protein was decreased significantly, while the expression of BAX, TNF-α, cleaved caspase-3, cleaved caspase-8, cleaved caspase-9 and cleaved PARP proteins was significantly increased in the pcDNA3.1-RBM5-treated mice as compared to that in the control mice.

Conclusions

In this study, we established a novel animal model to determine RBM5 function in vivo, and concluded that RBM5 inhibited tumor growth in mice by inducing apoptosis. The study suggests that although RBM5’s involvement in the death receptor-mediated apoptotic pathway is still to be investigated, RBM5-mediated growth suppression, at least in part, employs regulation of the mitochondrial apoptotic pathways.
Interaction of silicon-based quantum dots with gibel carp liver: oxidative and structural modifications
Authors: Stanca Loredana , Petrache Sorina Nicoleta , Serban Andreea Iren , Staicu Andrea Cristina , Sima Cornelia , Munteanu Maria Cristina , Zărnescu Otilia , Dinu Diana , Dinischiotu Anca
Published: May 2013

Quantum dots (QDs) interaction with living organisms is of central interest due to their various biological and medical applications. One of the most important mechanisms proposed for various silicon nanoparticle-mediated toxicity is oxidative stress. We investigated the basic processes of cellular damage by oxidative stress and tissue injury following QD accumulation in the gibel carp liver after intraperitoneal injection of a single dose of 2 mg/kg body weight Si/SiO2QDs after 1, 3, and 7 days from their administration.

QDs gradual accumulation was highlighted by fluorescence microscopy, and subsequent histological changes in the hepatic tissue were noted. After 1 and 3 days, QD-treated fish showed an increased number of macrophage clusters and fibrosis, while hepatocyte basophilia and isolated hepatolytic microlesions were observed only after substantial QDs accumulation in the liver parenchyma, at 7 days after IP injection.

Induction of oxidative stress in fish liver was revealed by the formation of malondialdehyde and advanced oxidation protein products, as well as a decrease in protein thiol groups and reduced glutathione levels. The liver enzymatic antioxidant defense was modulated to maintain the redox status in response to the changes initiated by Si/SiO2QDs. So, catalase and glutathione peroxidase activities were upregulated starting from the first day after injection, while the activity of superoxide dismutase increased only after 7 days. The oxidative damage that still occurred may impair the activity of more sensitive enzymes. A significant inhibition in glucose-6-phosphate dehydrogenase and glutathione-S-transferase activity was noted, while glutathione reductase remained unaltered.

Taking into account that the reduced glutathione level had a deep decline and the level of lipid peroxidation products remained highly increased in the time interval we studied, it appears that the liver antioxidant defense ofCarassius gibeliodoes not counteract the oxidative stress induced 7 days after silicon-based QDs exposure in an efficient manner.
Research on soybean curd coagulated by lactic acid bacteria
Authors: Jianming Wang , Qiuqian Lin , Yiyun Wang , Xi Chen
Published: May 2013

Chinese traditional soybean curd is coagulated by calcium salt. In order to investigate the feasibility of soybean curd coagulation by lactic acid bacteria, we studied the effective factors in soybean curd coagulation when using common soybean curd strains. In soybean curd concentration, incubating time and temperature as well as the inoculated amount and the edible gum additives were studied as the coagulating factors of soybean curd fermented by lactic acid bacteria. Based on the single factor and orthogonal experiment design, the optimized conditions of lactic acid bacteria fermentation curd was determined as follows: soybean curd concentration 12.5%(v/v)and the fermentation conducted at 42°C for 5 hours when the inoculating amount was 4.0% and edible gum additives was 1.4% (carrageenan 1.0% (m/v), soluble starch 0.4% (m/v)). Under the optimum conditions, the water-holding rate of the bean curd was measured as 69.82%, and the gel strength was 25.6 g/cm2. Compared with the traditional tofu coagulated by calcium salt, our products has less off-flavor and softer texture, which was accepted as new type of soybean curd according to the overall sensory evaluation
Selection of Immunostimulant AS15 for Active Immunization With MAGE-A3 Protein: Results of a Randomized Phase II Study of the European Organisation for Research and Treatment of Cancer Melanoma Group in Metastatic Melanoma
Authors: Kruit Wim H.J. , Suciu Stefan , Dreno Brigitte , Mortier Laurent , Robert Caroline , Chiarion-Sileni Vanna , Maio Michele , Testori Alessandro , Dorval Thierry , Grob Jean-Jacques , Becker Juergen C. , Spatz Alan , Eggermont Alexander M.M. , Louahed Jamila , Lehmann Frédéric F. , Brichard Vincent G. , Keilholz Ulrich
Published: May 2013

Purpose

Active immunization against the tumor-specific MAGE-A3 antigen is followed by a few but impressive and durable clinical responses. This randomized phase II trial evaluated two different immunostimulants combined with the MAGE-A3 protein to investigate whether a more robust and persistent immune response could be associated with increased clinical benefit.

Patients and Methods

Patients with MAGE-A3–positive stage III or IV M1a melanoma were randomly assigned to receive the MAGE-A3 protein combined either with AS02B or with AS15 immunostimulant. Clinical end points were toxicity and rates of objective clinical responses, progression-free survival (PFS), and overall survival (OS).

Results

Seventy-five patients were treated, with 36 eligible patients per arm. Both treatments were well tolerated. In the AS15 arm, four objective responses were observed (three complete responses and one partial response) versus one partial response in the AS02B arm. In the AS15 and AS02B arms, the PFS rates after 6 months were 25% and 14%, respectively; and the median OS times were 33 months and 19.9 months, respectively, with a median observation period of 48 months. Antibodies against MAGE-A3, found in all patients, showed three-fold higher titers in the AS15 arm. The anti–MAGE-A3 cellular response was also more pronounced in the AS15 arm.

Conclusion

In the MAGE-A3+AS15 arm, clinical activity was higher and the immune response more robust. Therefore, the AS15 immunostimulant was selected for combination with the MAGE-A3 protein in phase III trials.
Vagal Afferent NMDA Receptors Modulate CCK-Induced Reduction of Food Intake Through Synapsin I Phosphorylation in Adult Male Rats
Authors: Campos Carlos A. , Shiina Hiroko , Silvas Michael , Page Stephen , Ritter Robert C.
Published: May 2013

Vagal afferent nerve fibers transmit gastrointestinal satiation signals to the brain via synapses in the nucleus of the solitary tract (NTS). Despite their pivotal role in energy homeostasis, little is known about the cellular mechanisms enabling fleeting synaptic events at vagal sensory endings to sustain behavioral changes lasting minutes to hours. Previous reports suggest that the reduction of food intake by the satiation peptide, cholecystokinin (CCK), requires activation of N-methyl-D-aspartate-type glutamate receptors (NMDAR) in the NTS, with subsequent phosphorylation of ERK1/2 (pERK1/2) in NTS vagal afferent terminals. The synaptic vesicle protein synapsin I is phosphorylated by pERK1/2 at serines 62 and 67. This pERK1/2-catalyzed phosphorylation increases synaptic strength by increasing the readily releasable pool of the neurotransmitter. Conversely, dephosphorylation of serines 62 and 67 by calcineurin reduces the size of the readily releasable transmitter pool. Hence, the balance of synapsin I phosphorylation and dephosphorylation can modulate synaptic strength. We postulated that CCK-evoked activation of vagal afferent NMDARs results in pERK1/2-catalyzed phosphorylation of synapsin I in vagal afferent terminals, leading to the suppression of food intake. We found that CCK injection increased the phosphorylation of synapsin I in the NTS and that this increase is abolished after surgical or chemical ablation of vagal afferent fibers. Furthermore, fourth ventricle injection of an NMDAR antagonist or the mitogen-activated ERK kinase inhibitor blocked CCK-induced synapsin I phosphorylation, indicating that synapsin phosphorylation in vagal afferent terminals depends on NMDAR activation and ERK1/2 phosphorylation. Finally, hindbrain inhibition of calcineurin enhanced and prolonged synapsin I phosphorylation and potentiated reduction of food intake by CCK. Our findings are consistent with a mechanism in which NMDAR-dependent phosphorylation of ERK1/2 modulates satiation signals via synapsin I phosphorylation in vagal afferent endings.
The egg and the nucleus: a battle for supremacy
Authors: Gurdon J. B.
Published: May 2013

Sir John Gurdon and Professor Shinya Yamanaka were the recipients of the 2012 Nobel Prize for Physiology or Medicine. This Spotlight article is a commentary on the early nuclear transplant work in Xenopus, which was very important for the Nobel award in 2012, and the influence of this work on the reprogramming field.
Models of signalling networks – what cell biologists can gain from them and give to them
Authors: Janes Kevin A. , Lauffenburger Douglas A.
Published: May 2013

Computational models of cell signalling are perceived by many biologists to be prohibitively complicated. Why do math when you can simply do another experiment? Here, we explain how conceptual models, which have been formulated mathematically, have provided insights that directly advance experimental cell biology. In the past several years, models have influenced the way we talk about signalling networks, how we monitor them, and what we conclude when we perturb them. These insights required wet-lab experiments but would not have arisen without explicit computational modelling and quantitative analysis. Today, the best modellers are cross-trained investigators in experimental biology who work closely with collaborators but also undertake experimental work in their own laboratories. Biologists would benefit by becoming conversant in core principles of modelling in order to identify when a computational model could be a useful complement to their experiments. Although the mathematical foundations of a model are useful to appreciate its strengths and weaknesses, they are not required to test or generate a worthwhile biological hypothesis computationally.
Preparation of Wüstite Nanoparticles by a Solventless Synthetic Procedure
Authors: Nakaya Masafumi , Nishida Ryo , Muramatsu Atsushi
Published: May 2013

The novel synthetic procedure for wüstite nanoparticles with cubic shape was developed in the presence of a large amount of oleylamine and oleic acid against Fe precursor. The pretreatment under reduced pressure at 130 °C facilitated the formation of rather larger particles, 82 nm, by removing vapor during the reaction. The oxidation of FeO to Fe3O4 was precisely controlled so that the magnetic properties could be changed from paramagnetic to ferrimagnetic with the adjustment of the reaction time.
Synthesis and X-ray Structure of Endohedral Fullerene C60 Dimer Encapsulating a Water Molecule in Each C60 Cage
Authors: Zhang Rui , Murata Michihisa , Wakamiya Atsushi , Murata Yasujiro
Published: May 2013

Fullerene C60 dimers encapsulating one or two molecules of water in two C60 cages were newly synthesized, demonstrating almost no difference in chemical reactivity between empty C60 and H2O@C60. The X-ray structure of the doubly encapsulating dimer revealed the existance of the water molecules at the center of each C60 cage.
Murine Tim-1 is excluded from the immunological synapse
Authors: Lin Jean , Chen Leo , Kane Lawrence P
Published: May 2013

The interaction between T cells and APCs bearing cognate antigen results in the formation of an immunological synapse (IS). During this process, many receptors and signaling proteins segregate to regions proximal to the synapse. This protein movement is thought to influence T cell function. However, some proteins are transported away from the IS, which is controlled in part by ERM family proteins. Tim-1 is a transmembrane protein with co-stimulatory functions that is found on many immune cells, including T cells. However, the expression pattern of Tim-1 on T cells upon activation by APCs has not been explored. Interestingly, in this study we demonstrate that the majority of Tim-1 on activated T cells is excluded from the IS. Tim-1 predominantly resides outside of the IS, and structure/function studies indicate that the cytoplasmic tail influences Tim-1 polarization. Specifically, a putative ERM binding motif (KRK 244-246) in the Tim-1 cytoplasmic tail appears necessary for proper Tim-1 localization. Furthermore, mutation of the KRK motif results in enhanced early tyrosine phosphorylation downstream of TCR/CD28 stimulation upon ectopic expression of Tim-1. Paradoxically however, the KRK motif is necessary for Tim-1 co-stimulation of NFAT/AP-1 activation and co-stimulation of cytokine production. This work reveals unexpected complexity underlying Tim-1 localization and suggests potentially novel mechanisms by which Tim-1 modulates T cell activity.
FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells
Authors: Conrad Willliam , Major Michael B , Cleary Michele A , Ferrer Marc , Roberts Brian , Marine Shane , Chung Namjin , Arthur William T , Chien Andy J , Berndt Jason D , Moon Randall T
Published: May 2013

The inability of targeted BRAF inhibitors to produce long-lasting improvement in the clinical outcome of melanoma highlights a need to identify additional approaches to inhibit melanoma growth. Recent studies have shown that activation of the Wnt/β-catenin pathway decreases tumor growth and cooperates with ERK/MAPK pathway inhibitors to promote apoptosis in melanoma. Therefore, the identification of Wnt/β-catenin regulators may advance the development of new approaches to treat this disease. In order to move towards this goal we performed a large scale small-interfering RNA (siRNA) screen for regulators of β-catenin activated reporter activity in human HT1080 fibrosarcoma cells. Integrating large scale siRNA screen data with phosphoproteomic data and bioinformatics enrichment identified a protein, FAM129B, as a potential regulator of Wnt/β-catenin signaling.  Functionally, we demonstrated that siRNA-mediated knockdown of FAM129B in A375 and A2058 melanoma cell lines inhibits WNT3A-mediated activation of a β-catenin-responsive luciferase reporter and inhibits expression of the endogenous Wnt/β-catenin target gene, AXIN2. We also demonstrate that FAM129B knockdown inhibits apoptosis in melanoma cells treated with WNT3A. These experiments support a role for FAM129B in linking Wnt/β-catenin signaling to apoptosis in melanoma.
Analysis of impact of technological ways on economic area of world
Authors: Наташкина  , Natashkina E.
Published: May 2013

This article describes a distribution of technological ways, stages of life cycle, econometric analysis of their impact on economic area, process of substitution. Application model contribution of technological ways to the real GDP per capita by example of Denmark.
Sebaceous adenitis in dogs
Authors: Patel Anita
Published: May 2013

Sebaceous adenitis is a non-inflammatory condition characterised by scaling and alopecia. A predisposition is described in some breeds, such as the Standard Poodle and the Akita, but the condition can occur in any breed. The diagnosis is confirmed on histology, by demonstrating the presence of inflammatory cells targeting the sebaceous glands in the early stages of the disorder, or by the total absence of sebaceous glands in the end stage. Several management options are discussed in this paper.
Body condition scoring in dairy cattle: monitoring health to improve milk yield and fertility
Authors: Ohnstad Ian
Published: May 2013

Profitable dairy production relies on healthy cattle that convert feed efficiently into milk while maintaining good fertility. Body condition scoring, which makes an assessment of subcutaneous fat, can be used to reflect energy balance within the cow. It is essential to regularly score the body condition of dairy herds to ensure optimum health for fertility, calving and milk production, and to facilitate changes in management where necessary.
Tracheal collapse in a Shetland pony: a case study
Authors: Barakzai Safia
Published: May 2013

Tracheal collapse is most commonly reported in ponies and miniature horses, but can also occur in larger breeds of horses and ponies, as well as donkeys. Most develop clinical signs of tracheal collapse in middle age, indicating that some degenerative process of the tracheal cartilage or connective tissue may play a role in the pathogenesis of this disorder. This case study outlines the diagnosis, investigations and treatment options for tracheal collapse in a Shetland pony.
Medical Costs and Hospitalizations Among Patients with Depression Treated with Adjunctive Atypical Antipsychotic Therapy: An Analysis of Health Insurance Claims Data
Authors: Halpern Rachel , Nadkarni Anagha , Kalsekar Iftekhar , Nguyen Hiep , Song Rui , Baker Ross A , Nelson J Craig
Published: May 2013

BACKGROUND

Depression is frequently debilitating. The American Psychiatric Association recommends adjunctive atypical antipsychotics as a treatment option when response to antidepressants is inadequate.

OBJECTIVE

To compare medical costs and hospitalizations among patients with depression treated with adjunctive aripiprazole, olanzapine, or quetiapine.

METHODS

This retrospective analysis used medical and pharmacy claims data and enrollment information from a large US health plan. Patients were adult members of a commercial health plan who were diagnosed with depression (ie, ICD-9-CM 296.2x, 296.3x, or 311) and who received an antidepressant with adjunctive atypical antipsychotic therapy (aripiprazole, olanzapine, or quetiapine) between January 1, 2004, and January 31, 2010. Patients were continuously enrolled for 6-month pre- and 12-month postaugmentation periods. Those with schizophrenia or bipolar disorder were excluded. Postaugmentation outcomes were total and mental health–related medical costs and hospitalizations. Costs and hospitalizations were modeled with generalized linear models (ie, gamma distribution, log link) and logistic regression, respectively. Regressions controlled for dose, demographics, and general and medical health–related health status.

RESULTS

A total of 10,292 patients were identified across atypical antipsychotic cohorts: 3849 used aripiprazole, 1033 used olanzapine, and 5410 used quetiapine. Mean (SD) age was 44.1 (11.6) years and 70.3% were female. Compared with patients in the aripiprazole cohort, those in the olanzapine cohort had higher total medical costs (cost ratio [CR] 1.22, 95% CI 1.07–1.39) and higher mental health–related medical costs (CR 1.33, 95% CI 1.11–1.59), as well as higher odds of any (total) hospitalization (OR 1.58, 95% CI 1.30–1.92) and any mental health–related hospitalization (OR 1.81, 95% CI 1.38–2.38). Similarly, the quetiapine cohort had higher total medical costs (CR 1.27, 95% CI 1.16–1.39) and higher mental health–related medical costs (CR 1.23, 95% CI 1.09–1.39), as well as higher odds of any (total) hospitalization (OR 1.65, 95% CI 1.44–1.90) and any mental health–related hospitalizations (OR 1.78, 95% CI 1.45–2.18), compared with the aripiprazole cohort.

CONCLUSIONS

Compared with adjunctive olanzapine or quetiapine, adjunctive aripiprazole was associated with lower mean total and mental health–related medical costs and with lower odds of total and mental health–related hospitalizations in patients with depression.
Addition of Rifampin to Vancomycin for Methicillin-Resistant Staphylococcus aureus Infections: What Is the Evidence?
Authors: Tremblay Simon , Lau Tim TY , Ensom Mary HH
Published: May 2013

OBJECTIVE

To evaluate evidence supporting efficacy and safety of the combination of vancomycin and rifampin for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections.

DATA SOURCES

MEDLINE (1946-February 2013), EMBASE (1974-February 2013) and Cochrane Database of Systematic Reviews were searched.

STUDY SELECTION

All human prospective trials and retrospective studies evaluating clinical outcomes of vancomycin-rifampin combinations were included. Case reports, case series, and in vitro or animal data were excluded.

DATA EXTRACTION

Full-text articles were included and abstracts excluded; 43 of 421 references were reviewed. Five articles met inclusion and were evaluated.

DATA SYNTHESIS

A nonrandomized prospective trial reported complete clearance of MRSA bacteremia at 24 hours in all 14 burn patients receiving vancomycin-rifampin therapy. In a case-control study of 42 patients with MRSA endocarditis, adding rifampin prolonged bacteremia (5.2 vs 2.1 days, p < 0.001), decreased survival rates (79% vs 95%, p = 0.048), resulted in drug interactions (52% of cases), and increased hepatic transaminases (21% vs 2%, p = 0.014). In a retrospective analysis of 28 patients with persistent MRSA bacteremia requiring salvage therapy, switching from vancomycin-based to linezolid-based treatment was associated with better salvage success than adding rifampin (88% vs 0%, p < 0.001). In a randomized open-label trial of 42 patients with MRSA endocarditis, addition of rifampin to vancomycin did not affect cure rates (90% combination vs 82% monotherapy, p > 0.20), but increased duration of bacteremia (9 vs 7 days, p > 0.20) compared with vancomycin monotherapy. Another randomized open-label trial of combination versus monotherapy for MRSA pneumonia in 93 intensive care unit patients reported higher clinical successes (53.7% vs 31.0%, p = 0.047), similar 30-day mortality rates, and more adverse events with combination therapy (11 vs 6).

CONCLUSIONS

Limited evidence exists to support the adjunctive use of rifampin to treat MRSA infections. The combination may increase drug interactions, adverse effects, and rifampin resistance. Further studies are needed to define the role of rifampin adjunct therapy.
Nepafenac: An Ophthalmic Nonsteroidal Antiinflammatory Drug for Pain After Cataract Surgery
Authors: Jones Benjamin M , Neville Michael W
Published: May 2013

OBJECTIVE:

To examine the efficacy of nepafenac in the treatment of pain and inflammation in patients after cataract surgery using evidence from controlled clinical studies.

DATA SOURCES:

Citations in Google Scholar, PubMed, and Web of Science from January 1, 2005, to March 25, 2013, were identified using nepafenac and cataract as search terms.

STUDY SELECTION AND DATA EXTRACTION:

The literature search was limited to human studies published in English. Three trials that compared nepafenac with other nonsteroidal antiinflammatory drugs (NSAIDs) were included.

DATA SYNTHESIS:

The pharmacokinetics and pharmacodynamics of nepafenac 0.1% suspension (and its active metabolite, amfenac) were compared with bromfenac 0.09% solution and ketorolac 0.4% solution with respect to aqueous humor concentrations and ability to reduce cyclooxygenase 1 and 2 (COX-1 and COX-2) enzymes. The maximum concentration (Cmax) values of ketorolac and amfenac were statistically similar, while the Cmax of bromfenac was significantly lower than that of amfenac. Ketorolac most effectively inhibited COX-1 enzymes; COX-2 enzymes were most effectively reduced by amfenac. When nepafenac 0.1% suspension was compared with placebo and ketorolac 0.5% solution, nepafenac achieved a higher percentage cure rate than placebo at day 14 (p = 0.0241). Significant differences in cure rates between nepafenac and ketorolac were not observed. Nepafenac 0.1%, bromfenac 0.09%, and ketorolac 0.45% were compared to determine which most effectively reduced prostaglandin E2 (PGE2) following surgery. PGE2 concentrations were significantly lowest in the ketorolac group, followed by the bromfenac and nepafenac groups, respectively. Topical nepafenac 0.1% suspension was approved in 2005. A 0.3% suspension was approved in October 2012. The 0.3% product may have some advantages over its predecessor: it is dosed once rather than thrice daily, which may increase patient adherence and improve outcomes. The price and dosing frequency of the 0.3% product are comparable to those of bromfenac 0.09% solution.

CONCLUSIONS:

The 2 nepafenac products appear to be equally efficacious, with a slightly increased adverse event rate in patients using the 0.3% versus 0.1% formulation. Head-to-head clinical trials that compare the 0.3% product with the 0.1% product or other commercially available NSAIDs are unavailable.
Linezolid Desensitization for a Patient with Multiple Medication Hypersensitivity Reactions
Authors: Bagwell Autumn D , Stollings Joanna L , White Katie D , Fadugba Olajumoke O , Choi Jane J
Published: May 2013

OBJECTIVE

To describe a case in which a linezolid desensitization protocol was successfully used for a polymicrobial surgical wound infection in a patient with multiple drug hypersensitivity reactions.

CASE SUMMARY

A 24-year-old woman with vocal cord dysfunction requiring tracheostomy was admitted for a surgical wound infection following a tracheostomy fistula closure procedure. The patient reported multiple antibiotic allergies including penicillins (rash), sulfonamides (rash), vancomycin (anaphylaxis), azithromycin (rash), cephalosporins (anaphylaxis), levofloxacin (unspecified), clindamycin (unspecified), and carbapenems (unspecified). Gram stain of the purulent wound drainage demonstrated mixed gram-negative and gram-positive flora, and bacterial cultures were overgrown with Proteus mirabilis, which precluded identification of other pathogens. Following failed test doses of linezolid, tigecycline, and daptomycin, all of which resulted in hypersensitivity reactions, a 16-step linezolid desensitization protocol was developed and successfully implemented without adverse reactions. The patient completed a 2-week course of antibiotic therapy that included linezolid upon finishing the desensitization protocol.

DISCUSSION

Linezolid is useful in treating complicated and uncomplicated skin and soft tissue infections caused by gram-positive bacteria. With precautions, including premedication, a monitored nursing unit, and immediate availability of an emergency anaphylaxis kit, drug desensitization allows patients the ability to safely use medications to which they may have an immediate hypersensitivity reaction. Minimal data exist on linezolid desensitization protocols.

CONCLUSIONS

Linezolid desensitization can be a viable option in patients requiring antimicrobial therapy for complicated gram-positive skin infections.
Peripheral Deafferentation-Driven Functional Somatosensory Map Shifts Are Associated with Local, Not Large-Scale Dendritic Structural Plasticity
Authors: Schubert Vanessa , Lebrecht Daniel , Holtmaat Anthony
Published: May 2013

Long-term peripheral deafferentation induces representational map changes in the somatosensory cortex. It has been suggested that dendrites and axons structurally rearrange in such paradigms. However, the extent and process of this plasticity remains elusive. To more precisely quantify deafferentation-induced structural plasticity of excitatory cells we repeatedly imaged GFP-expressing L2/3 and L5 pyramidal dendrites in the mouse barrel cortex over months after the removal of a subset of the whisker follicles (FR), a procedure that completely and permanently removes whisker-sensory input. In the same mice we imaged whisker-evoked intrinsic optical signals (IOS) to assess functional cortical map changes. FR triggered the expansion of spared whisker IOS responses, whereas they remained unchanged over months in controls. The gross structure and orientation of apical dendrite tufts remained stable over a two-month period, both in controls and after deprivation. However, terminal branch tip dynamics were slightly reduced after FR, and the formation of new dendritic spines was increased in a cell-type and location-dependent manner. Together, our data suggest that peripheral nerve lesion-induced cortical map shifts do not depend on the large scale restructuring of dendritic arbors but are rather associated with local cell-type and position-dependent changes in dendritic synaptic connectivity.
Spontaneous Brain Activity Predicts Learning Ability of Foreign Sounds
Authors: Ventura-Campos Noelia , Sanjuán Ana , González Julio , Palomar-García María-Ángeles , Rodríguez-Pujadas Aina , Sebastián-Gallés Núria , Deco Gustavo , Ávila César
Published: May 2013

Can learning capacity of the human brain be predicted from initial spontaneous functional connectivity (FC) between brain areas involved in a task? We combined task-related functional magnetic resonance imaging (fMRI) and resting-state fMRI (rs-fMRI) before and after training with a Hindi dental–retroflex nonnative contrast. Previous fMRI results were replicated, demonstrating that this learning recruited the left insula/frontal operculum and the left superior parietal lobe, among other areas of the brain. Crucially, resting-state FC (rs-FC) between these two areas at pretraining predicted individual differences in learning outcomes after distributed (Experiment 1) and intensive training (Experiment 2). Furthermore, this rs-FC was reduced at posttraining, a change that may also account for learning. Finally, resting-state network analyses showed that the mechanism underlying this reduction of rs-FC was mainly a transfer in intrinsic activity of the left frontal operculum/anterior insula from the left frontoparietal network to the salience network. Thus, rs-FC may contribute to predict learning ability and to understand how learning modifies the functioning of the brain. The discovery of this correspondence between initial spontaneous brain activity in task-related areas and posttraining performance opens new avenues to find predictors of learning capacities in the brain using task-related fMRI and rs-fMRI combined.
Blindleistungsregelung von WEA im Netzparallelbetrieb
Authors: Fortmann Jens , Erlich István
Published: May 2013

Die Spannungs-Blindleistungsanforderungen von Windparks sind vergleichbar mit denen von konventionellen Kraftwerken. Einerseits sollten WEA die Blindleistungsregelung an die wechselnden Lastflussbedingungen entsprechend einer vordefinierten Charakteristik des Netzes anpassen. Die Antwortzeit dieser langsamen Regelung ist ca. 10 bis 60 Sekunden und muss mit den Reaktion anderer Blindleistungsquellen koordiniert werden um eine optimale Blindleistungseinspeisung zu erzielen. Andrerseits ist im Fall plötzlicher Spannungseinbrüche eine Spannungsstützung durch Blindstromeinspeisung innerhalb von 20–30 m notwendig. Auf der Grundlage einer Analyse der Netzanforderungen wird in diesem Beitrag ein hierarchisches Regelungskonzept für die Blindleistungsregelung von WEA und Windparks dargestellt. Das Regelungsschema ist in der Lage, sowohl die langsamen als auch die schnellen Anforderungen ohne die Notwendigkeit einer Strukturumschaltung zwischen unterschiedlichen Teilen der Regelung oder durch ein Totband, wie in manchen Netzanschlussregeln vorgeschlagen, zu erfüllen. Die Simulationsbeispiele zeigen sowohl die stationären Regelanforderungen als auch die Antwort auf einen Kurzschluss im übergeordneten Netz für einen realistischen Windpark.
The role of 18F-fluorodeoxyglucose positron emission tomography in differentiated thyroid cancer before surgery
Authors: Pak Kyoungjune , Kim Seong-Jang , Kim In Joo , Kim Bo Hyun , Kim Sang Soo , Jeon Yun Kyung
Published: May 2013

The incidence of thyroid cancer in both men and women is increasing faster than that of any other cancer. Although positron emission tomography (PET) using18F-fluorodeoxyglucose (FDG) has received much attention, the use of FDG PET for the management of thyroid cancer is limited primarily to postoperative follow-up. However, it might have a role in selected, more aggressive pathologies, and so patients at a high risk of distant metastasis may benefit from PET before surgery. As less FDG-avid thyroid cancers may lower the diagnostic accuracy of PET in preoperative assessment, an understanding of FDG avidity is important for the evaluation of thyroid cancer. FDG avidity has been shown to be associated with tumor size, lymph node metastasis, and glucose transporter expression and differentiation. As PET is commonly used in clinical practice, the detection of incidentalomas by PET is increasing. However, incidentalomas detected by PET have a high risk of malignancy. Clinicians handling cytologically indeterminate nodules face a dilemma regarding a procedure for a definitive diagnosis, usually lobectomy. With ‘nondiagnostic (ND)’ fine-needle biopsy (FNA), PET has shown a negative predictive value (NPV) of 100%, which indicates that negative uptake in a ND FNA procedure accurately excludes malignancy. With ‘atypia of undetermined significance’ or ‘follicular neoplasm’, the sensitivity and NPV of PET are 84 and 88%. PET does not provide additional information for the preoperative assessment of thyroid cancer. However, factors associated with FDG positivity are related to a poor prognosis; therefore, FDG PET scans before surgery may facilitate the prediction of the prognosis of differentiated thyroid cancer.
Genetic Structure and Linkage Disequilibrium in a Diverse, Representative Collection of the C4 Model Plant, Sorghum bicolor
Authors: Wang Yi-Hong , Upadhyaya Hari D , Burrell A Millie , Sahraeian Sayed Mohammad Ebrahim , Klein Robert R , Klein Patricia E
Published: May 2013

To facilitate the mapping of genes in sorghum [Sorghum bicolor (L.) Moench] underlying economically important traits, we analyzed the genetic structure and linkage disequilibrium in a sorghum mini core collection of 242 landraces with 13,390 single-nucleotide polymorphims. The single-nucleotide polymorphisms were produced using a highly multiplexed genotyping-by-sequencing methodology. Genetic structure was established using principal component, Neighbor-Joining phylogenetic, and Bayesian cluster analyses. These analyses indicated that the mini-core collection was structured along both geographic origin and sorghum race classification. Examples of the former were accessions from Southern Africa, East Asia, and Yemen. Examples of the latter were caudatums with widespread geographical distribution, durras from India, and guineas from West Africa. Race bicolor, the most primitive and the least clearly defined sorghum race, clustered among other races and formed only one clear bicolor-centric cluster. Genome-wide linkage disequilibrium analyses showed linkage disequilibrium decayed, on average, within 10−30 kb, whereas the short arm of SBI-06 contained a linkage disequilibrium block of 20.33 Mb, confirming a previous report of low recombination on this chromosome arm. Four smaller but equally significant linkage disequilibrium blocks of 3.5−35.5 kb were detected on chromosomes 1, 2, 9, and 10. We examined the genes encoded within each block to provide a first look at candidates such as homologs of GS3 and FT that may indicate a selective sweep during sorghum domestication.
Identification of Null Alleles and Deletions from SNP Genotypes for an Intercross Between Domestic and Wild Chickens
Authors: Crooks Lucy , Carlborg Örjan , Marklund Stefan , Johansson Anna M
Published: May 2013

We analyzed genotypes from ~10K single-nucleotide polymorphisms (SNPs) in two families of an F2 intercross between Red Junglefowl and White Leghorn chickens. Possible null alleles were found by patterns of incompatible and missing genotypes. We estimated that 2.6% of SNPs had null alleles compared with 2.3% with genotyping errors and that 40% of SNPs in which a parent and offspring were genotyped as different homozygotes had null alleles. Putative deletions were identified by null alleles at adjacent markers. We found two candidate deletions that were supported by fluorescence intensity data from a 60K SNP chip. One of the candidate deletions was from the Red Junglefowl, and one was present in both the Red Junglefowl and White Leghorn. Both candidate deletions spanned protein-coding regions and were close to a previously detected quantitative trait locus affecting body weight in this population. This study demonstrates that the ~50K SNP genotyping arrays now available for several agricultural species can be used to identify null alleles and deletions in data from large families. We suggest that our approach could be a useful complement to linkage analysis in experimental crosses.
Topics in Neonatal Informatics
Authors: Lehmann Christoph U. , Shorte Vanessa , Gundlapalli Adi V.
Published: May 2013

Increased funding for health information technology and the advance of electronic health records in hospitals and practices have created the need for a new specialist: the clinical informatician. Clinical informatics was recognized in 2011 as the latest subspecialty in medicine by the American Board of Medical Specialties. This article reviews the need for this new specialty as well as the steps necessary for its creation. The content and training requirements for clinical informatics are discussed as well as eligibility criteria for taking the board examination. Training programs as well as board preparation are addressed along with the expected impact that this new field will have on the practice of medicine.
Pediatric Collaborative Improvement Networks: Background and Overview
Authors: Lannon Carole M. , Peterson Laura E.
Published: May 2013

Multiple gaps exist in health care quality and outcomes for children, who receive <50% of recommended care. The American Board of Pediatrics has worked to develop an improvement network model for pediatric subspecialties as the optimal means to improve child health outcomes and to allow subspecialists to meet the performance in practice component of Maintenance of Certification requirements. By using successful subspecialty initiatives as exemplars, and features of the Institute for Healthcare Improvement’s Breakthrough Series model, currently 9 of 14 pediatric subspecialties have implemented collaborative network improvement efforts. Key components include a common aim to improve care; national multicenter prospective collaborative improvement efforts; reducing unnecessary variation by identifying, adopting, and testing best practices; use of shared, valid, high-quality real-time data; infrastructure support to apply improvement science; and public sharing of outcomes. As a key distinguisher from time-limited collaboratives, ongoing pediatric collaborative improvement networks begin with a plan to persist until aims are achieved and improvement is sustained. Additional evidence from within and external to health care has accrued to support the model since its proposal in 2002, including the Institute of Medicine’s vision for a Learning Healthcare System. Required network infrastructure systems and capabilities have been delineated and can be used to accelerate the spread of the model. Pediatric collaborative improvement networks can serve to close the quality gap, engage patients and caregivers in shared learning, and act as laboratories for accelerated translation of research into practice and new knowledge discovery, resulting in improved care and outcomes for children.
Level Set Modeling of Nickel Silicide Growth
Authors: Kumar Ashish , Law Mark E.
Published: May 2013

Level set methods have been used for Solid phase epitaxial regrowth, etching and deposition.This study is to model the growth of nickel silicide accurately using the level set method. NiSi growth has been observed to follow a linear-parabolic law which takes into account both diffusion and interfacial reaction. This linear-parabolic system is very similar to the Deal and Grove model of SiO2 growth. This model uses similar diffusion transport and reaction rate equations. This simulation models the growth of silicide coupling diffusion solutions to level-set techniques. Dual level sets have been used for top and bottom interface propagation of silicide; velocities were estimated based on nickel concentrations at both interfaces as well as diffusivity and reaction rate of nickel. This is important to predict precise shape of silicide that will allow current crowding and field focusing effects to be modeled in transport out of the intrinsic device into the contacting layers. These simulation models can be used for latest technology nodes at 45, 32, 22nm and special devices such as FinFET’s etc. The level set method is successfully implemented and verified in Florida Object Oriented Process Simulator and growth shapes matches well with the literature Transmission Electron Microscopy data.
Electrical Contact Characteristics between Silicon Micropillars and Ag Nanoparticles with Controlled Mechanical Load
Authors: Logeeswaran VJ , Triplett Mark , Lam Daniel , Yengel Emre , Grewal Heim , Ombaba Matthew , Islam M. Saif
Published: May 2013

We report an experimental investigation on employing Ag nanoparticles to provide electrical and mechanical contacts between transfer-printed semiconductor devices in the shape of micro/nano- wires and pillars. The Ag nanoparticles have diameters ranging between 200-800nm and are assembled on a 200nm Au film deposited on glass substrates. With a customized tool, an ensemble of silicon pillars were brought into contact with the silver (Ag) nanoparticles (AgNPs) by precisely controlling the displacement and applied force (pressure). Current-voltage measurements were done at force resolution of ~0.2N. The test method aims to illuminate the pillar-particle contact mechanism using the nanoparticles as conductive fillers for the next generation of high performance heteroepitaxial device transfer-printing applications.
Metadislocations: The case of pure glide
Authors: Heggen Marc , Feuerbacher Michael
Published: May 2013

Metadislocations are highly complex and pivotal defects mediating plastic deformation in complex metallic alloys. Here, we review recent results on the structure of metadislocations in the phases T-Al-Mn-Pd, T-Al-Mn-Fe and o-Al13Co4. In these materials, metadislocation motion is of particular interest as it takes place by pure glide in contrast to most other complex metallic alloys. Recently, novel metadislocations were found in the T-phase [1]. They have Burgers vectors${\rm{\vec b}} = \pm \tau ^{ - n} c\left( {\matrix{ 0 & 0 & 1 \cr } } \right)$(n = 2, 3, 4) and are associated to two, four and six planar defects, respectively. The type of planar defect depends on the deformation geometry. Metadislocation glide creates (1 0 0) stacking faults and climb creates (0 0 1) phason planes. Metadislocation glide was observed in the o-Al13Co4phase, as well [2]. The close structural relation of metadislocations in the phases T-Al-Mn-Pd, T-Al-Mn-Fe, Al13Co4and ε6-Al-Pd-Mn is discussed.
The Fragmentation of Al-W Granular Composites Under Explosive Loading
Authors: Olney Karl L. , Chiu Po-Hsun , Nesterenko Vitali F. , Benson David J. , Braithwaite Chris , Collins Adam , Williamson David , McKenzie Francesca
Published: May 2013

Small scale explosively driven fragmentation experiments have been performed on Aluminum (Al)-Tungsten (W) granular composite rings processed using cold isostatic compression of Al and W powders with a particle size of 4-30 microns. Fragments collected from the experiments had a maximum size of the order of a few hundred micrometers. This is a dramatic reduction in the fragment size when compared to the 1-10 mm typical for a homogeneous material such as solid aluminum under similar loading conditions. Numerical simulations of the experiment were performed to elucidate the mechanisms of fragmentation that were responsible for this shift in fragmentation size scales. Simulations were performed with a significantly stronger explosive driver to examine how the mechanisms of fragmentation change when the detonation pressure increases.
Cascade Overlap in hcp Zirconium: Defect Accumulation and Microstructure Evolution with Radiation using Molecular Dynamics Simulations
Authors: Nandi Prithwish K. , Eapen Jacob
Published: May 2013

Molecular dynamics simulations are performed to investigate the defect accumulation and microstructure evolution in hcp zirconium (Zr) – a material which is widely used as clad for nuclear fuel. Cascades are generated with a 3 keV primary knock-on atom (PKA) using an embedded atom method (EAM) potential with interactions modified for distances shorter than 0.1 Å. With sequential cascade simulations we show the emergence of stacking faults both in the basal and prism planes, and a Shockley partial dislocation on the basal plane.
Fourier Transform Infrared Imaging to Elucidate Failures in Polyurethanes
Authors: Miseo Ellen V. , Powell Jay R.
Published: May 2013

Polyurethanes are widely used, from medical devices to electrical materials to consumer goods. These materials have chemical stability issues which impact the mechanical stability. Infrared micro spectroscopy has been used to study polyurethane degradation, but due to experimental limitations, samples examined were no smaller than approximately 15 microns on a side. Because of the complex chemistry of urethanes, chemical examination of the material on a much higher spatial resolution scale would be valuable.

A relatively new technique, Attenuated Total Reflection Fourier Transform Infrared Spectrochemical MicroImaging has been used to examine degraded polyester urethanes. Rather than using a single-element detector, a two dimensional array detector generates thousands of spectra simultaneously. In addition, a germanium prism generates a magnification effect; resulting in a significantly higher spatial resolution. The net output of the analysis is a hypercube of high resolution infrared spectra showing urethane degradation progression on a much smaller spatial scale than was previously possible.
Reduction of Gd6UO12 for the Synthesis of Gd6UO11
Authors: Pieck Darío , Desgranges Lionel , Pontillon Yves , Matheron Pierre
Published: May 2013

In the present work, we focus on δ-Gd6UO12 phase and its stability under reducing conditions. This later point is interesting regarding reducing environment that could exist in some nuclear storage sites and that could possibly degrade δ–compounds. A polycrystalline δ-Gd6UO12 sample was prepared by sintering cubic-Gd2O3 and UO2 mixed powders under an air atmosphere. The resulting pellets were then characterized and reduced by heat treatment under an Ar with H2 5% atmosphere. XRD analysis of the sample after reduction did not confirm the reduction into Gd6UO11 but a decomposition of the δ-compound. Preliminary characterizations of these decomposition products are presented.