bluuebunny/crossref_metadata_2025 huggingface dataset:
Femoral Artery Pseudoaneurysm and Sudden Death
Authors: Zhou Chong , Langlois Neil E. , Byard Roger W.
Published: August 2011

Abstract:  Pseudoaneurysm formation may be a late complication of vascular grafting. A case of sudden death in an 83‐year‐old woman with a previous aortobifemoral bypass graft is reported that was due to spontaneous hemorrhage from a pseudoaneurysm of the graft site that had eroded through the overlying skin and subcutaneous tissues. Pseudoaneuryms do not have to be of a particularly large size for rupture to occur. Social isolation and age‐related cognitive impairment may delay treatment in older individuals resulting in a lethal outcome. The elderly are also more vulnerable to serious morbidity and death under these circumstances owing to significant underlying cardiovascular and respiratory disease and/or anticoagulant medication. Rarer conditions that may cause pseudoaneurysms include tumors and vasculidites. The possibility of an infectious contribution to the pseudoaneurysm should be considered and microbiological sampling undertaken.
Trauma, exile and mental health in young refugees
Authors: Montgomery E.
Published: August 2011

Montgomery E. Trauma, exile and mental health in young refugees.

Objective: To review evidence of trauma and exile‐related mental health in young refugees from the Middle East.

Method: A review of four empirical studies: i) a qualitative study of 11 children from torture surviving families, ii) a cohort study of 311 3–15‐year‐old asylum‐seeking children, iii) a qualitative study of 14 members of torture surviving families and iv) a follow‐up study of 131 11–23‐year‐old refugees.

Results: The reactions of the children were not necessarily post‐traumatic stress disorder specific. Seventy‐seven per cent suffered from anxiety, sleep disturbance and/or depressed mood at arrival. Sleep disturbance (prevalence 34%) was primarily predicted by a family history of violence. At follow‐up, 25.9% suffered from clinically relevant psychological symptoms. Traumatic experiences before arrival and stressful events in exile predicted internalizing behaviour, witnessing violence and frequent school changes in exile predicted externalizing behaviour. School participation, Danish friends, language proficiency and mother’s education predicted less long‐term psychological problems.

Conclusion: Psychological problems are frequent in refugee children, but the extents are reduced over time in exile. Traumatic experience before arrival is most important for the short‐term reaction of the children while aspects of life in exile are important for the children’s ability to recover from early traumatization.
Unexpected mechanisms sustain the stress gradient hypothesis in a tropical alpine environment
Authors: Anthelme Fabien , Buendia Belen , Mazoyer Charlotte , Dangles Olivier
Published: August 2011

Questions

Does facilitation among plants increase with elevation in a humid tropical alpine system in which climatic and ecological conditions differ from other alpine environments? What mechanisms are involved in the interactions?

Location

Volcano Antisana, Eastern Cordillera of the Ecuadorian Andes (00°28′S, 78°09′W).

Methods

We selected the cushion‐forming Azorella aretioides as a potential nurse plant along an altitudinal gradient (4400, 4550 and 4700 m) in the high tropical Andes. We quantified its effects on other plants at species and community levels by comparing the product vegetation cover × number of individuals of every vascular species found inside and outside 265 cushions, using the relative interaction index. We inferred potential mechanisms behind the interactions through analysis of microclimate, soil moisture and soil nutrient measurements inside and outside cushions.

Results

Predictions of the stress gradient hypothesis (SGH) were corroborated at community level, with transition from competitive or neutral effects of A. aretioides at 4400 and 4550 m to facilitative effects at 4700 m. Strong species‐specific effects were observed along the altitudinal gradient, with a substantial effect of local habitat disturbance on the outcome of plant–plant interactions. Surprisingly, cushions lowered air and soil temperatures and air humidity, which reduced at higher elevations. Facilitation appeared to be caused by higher soil moisture and nutrient content beneath cushions.

Conclusions

Our data extend the framework of the SGH by corroborating it for the first time in a tropical alpine system. However, the mechanisms underlying plant–plant interactions differed from those generally reported from alpine environments, with facilitation varying according to resource‐mediated stress (nutrients). It remains to be tested whether this is specific to tropical alpine systems.
Variation of the γ opacity by the He II Lyman continuum constrains the location of the γ-ray emission region in the blazar 3C 454.3
Authors: Stern Boris E. , Poutanen Juri
Published: August 2011

We study spectral properties of the brightest γ-ray blazar 3C 454.3 using 138 weeks of observations by the Fermi Gamma-ray Space Telescope (Fermi). We probe the behaviour of the source as a function of time at different brightness levels. The Fermi spectra in the GeV range can be well described by a wide underlying lognormal distribution with the photon—photon absorption breaks produced by the He ii and H i Lyman recombination continua (LyC). We find a power-law dependence of the peak energy on flux and discover anticorrelation between the column density of the He ii LyC and flux. This implies that the γ-ray emission zone lies close to the boundary of the high-ionization part of the broad-line region and moves away from the black hole when the flux increases. Identification of the γ-ray production with the relativistic jet implies that the jet is already accelerated at sub-parsec distances from the central black hole, which favours the Blandford—Znajek process as the jet launching mechanism.
Ancient giants: on the farthest galaxy at z = 8.6
Authors: Dayal Pratika , Ferrara Andrea
Published: August 2011

The observational frontiers for the detection of high-redshift galaxies have recently been pushed to unimaginable distances with the record-holding Lyman alpha emitter (LAE) UDFy-38135539 discovered at redshift z= 8.6. However, the physical nature and the implications of this discovery have yet to be assessed. By selecting galaxies with observed luminosities similar to UDFy-38135539 in state-of-the-art cosmological simulations tuned to reproduce the large-scale properties of LAEs, we bracket the physical nature of UDFy-38135539: it has a star formation rate ∼2.7–3.7 M⊙ yr−1, it contains 108.3-8.7 M⊙ of stars 50–80 Myr old, with stellar metallicity ∼0.03–0.12 Z⊙. For any of the simulated galaxies to be visible as a LAE in the observed range, the intergalactic neutral hydrogen fraction at z= 8.6 must be χH I≤ 0.2 and extra ionizing radiation from sources clustered around UDFy-38135539 is necessary. Finally, we predict that there is a 70 per cent (15 per cent) probability of detecting at least one such source from JWST (HST/WFC3) observations in a physical radius ∼0.4 Mpc around UDFy-38135539.
Computational‐Aided Design for Dopamine Prodrugs Based on Novel Chemical Approach
Authors: Karaman Rafik
Published: August 2011

The goal of this project was to design novel dopamine prodrugs for the treatment of Parkinson’s disease that can improve the overall biopharmaceutical profile of the current medications to enhance effectiveness and to ease the use of the medications. Based on Menger’s study and other’s kinetic studies on the cleavage reactions of some Kemp’s acid amides to the corresponding amines and anhydrides, DFT calculations were made to find a candidate to be used as an efficient dopamine prodrug. The proposed dopamine prodrugs have a carboxylic group as a hydrophilic moiety and a hydrocarbon skeleton as a lipophilic moiety, where the combination of both groups ensures a moderate hydrophilic lipophilc balance value. The potential prodrugs are expected to give better bioavailability than the parental drug owing to improved absorption. Furthermore, the proposed prodrugs are believed to be more effective than l‐dopa because the latter undergoes decarboxylation in the periphery before reaching the blood–brain barrier. Additionally, the predicted prodrugs can be used in different dosage forms (I.V., S.C., tablets, and others) because of their potential solubility in organic and aqueous media. It is expected that the proposed prodrugs will undergo cleavage reactions to release the parental dopamine drug with half‐life time (t½) of 12–20 h.
1‐[(2‐Arylthiazol‐4‐yl)methyl]azoles as a New Class of Anticonvulsants: Design, Synthesis, In vivo Screening, and In silico Drug‐like Properties
Authors: Ahangar Nematollah , Ayati Adile , Alipour Eskandar , Pashapour Arsalan , Foroumadi Alireza , Emami Saeed
Published: August 2011

A series of novel thiazole incorporated (arylalkyl)azoles were synthesized and screened for their anticonvulsant properties using maximal electroshock and pentylenetetrazole models in mice. Among target compounds, 1‐[(2‐(4‐chlorophenyl)thiazol‐4‐yl)methyl]‐1H‐imidazole (compound 4b), 1‐[(2‐phenylthiazol‐4‐yl)methyl]‐1H‐1,2,4‐tria‐zole (8a), and its 4‐chlorophenyl analog (compound 8b) were able to display noticeable anticonvulsant activity in both pentylenetetrazole and maximal electroshock tests with percentage protection range of 33–100%. A computational study was carried out for prediction of pharmacokinetics properties and drug‐likeness. The structure‐activity relationship and in silico drug relevant properties (molecular weight, topological polar surface area, clog P, hydrogen bond donors, hydrogen bond acceptors, and log BB) confirmed that the compounds were within the range set by Lipinski’s rule‐of‐five, and possessing favorable physicochemical properties for acting as CNS‐drugs, making them potentially promising agents for epilepsy therapy.
Antifungal Agents. Part 3: Synthesis and Antifungal Activities of 3‐Acylindole Analogs against Phytopathogenic Fungi In Vitro
Authors: Xu Hui , bin Yang Wen , Wang Qin
Published: August 2011

To find more potent antifungal compounds, twenty 3‐acylindole analogs were synthesized and bio‐evaluated for their antifungal activities against seven phytopathogenic fungi. Structure–activity relationships investigations revealed that 4‐ or 6‐methyl and 3‐acetyl or propionyl groups were the important structural properties of 3‐acylindoles for the activities. Especially 4‐methyl‐3‐propionylindole, 12, displayed the more potent activities than hymexazol, a commercially available agricultural fungicide, and might be considered as a new promising lead candidate for further design and synthesis of agricultural fungicides.
The regulation of blood perfusion in the renal cortex and medulla by reactive oxygen species and nitric oxide in the anaesthetised rat
Authors: Ahmeda A. F. , Johns E. J.
Published: August 2011

Aims:  The regulation of blood flow through the renal medulla is important in determining blood pressure, and its dysregulation in pathophysiological states, such as oxidative stress, may contribute to the development of hypertension. This investigation examined the hypothesis that reactive oxygen species has both direct and indirect actions, via scavenging NO, to determine the degree of blood perfusion through the renal medulla.

Methods:  Groups of male Wistar rats received a renal interstitial infusion of either tempol, a superoxide dismutase (SOD) mimetic, or tempol plus catalase (tem + cat), or diethyldithio‐carbamic acid (DETC) a SOD inhibitor, or L‐NAME alone or L‐NAME followed by DETC.

Results:  Medullary blood perfusion (MBP) increased by 16 ± 1% (P < 0.05) following the renal infusion of tempol and by 35 ± 4%% (P < 0.05) when tem + cat was infused. Cortical blood perfusion (CBP) was unchanged during the administration of tempol and tem + cat. The renal interstitial infusion of DETC reduced CBP by 13 ± 2%, (P < 0.05) and MBP by 22 ± 3% (P < 0.05). Infusion of L‐NAME to block NOS did not change CBP but decreased MBP by 12 ± 4%, which was (P < 0.05) less than the reduction obtained with DETC. Administration of DETC in the presence of L‐NAME reduced CBP and MBP by 17 and 14%, respectively, the latter response being approximately half that obtained when only DETC was infused.

Conclusions:  These findings demonstrated that both reactive oxygen species and NO determined the level of MBP. The findings support the hypothesis that reactive oxygen species can act both indirectly, via scavenging of NO, and directly via H2O2 to modulate blood perfusion in the medulla.
Interplay of endothelial and inducible nitric oxide synthases modulates the vascular response to ischaemia–reperfusion in the rabbit lung
Authors: Sedoris K. C. , Gozal E. , Ovechkin A. V. , Theile A. R. , Roberts A. M.
Published: August 2011

Aim:  Lung ischaemia–reperfusion induces nitric oxide synthesis and reactive nitrogen species, decreasing nitric oxide bioavailability. We hypothesized that in the ventilated lung, this process begins during ischaemia and intensifies with reperfusion, contributing to ischaemia–reperfusion‐induced pulmonary vasoconstriction. The aim was to determine whether ischaemia–reperfusion alters inducible and endothelial nitric oxide synthase expression/activity, reactive nitrogen species generation, and nitric oxide bioavailability, potentially affecting pulmonary perfusion.

Methods:  Ischaemia–reperfusion was induced for various times in anesthetized rabbits with ventilated lungs by reversibly occluding the right pulmonary artery and initiating reperfusion. Nitric oxide synthase activity/expression and phosphorylation, reactive nitrogen species generation and total nitrate/nitrite were determined in lung tissue.

Results:  Inducible nitric oxide synthase expression and activity, and reactive nitrogen species formation coincided with increased pulmonary vascular resistance during reperfusion and increased with ischaemia duration, further increasing after 2‐h reperfusion. Total nitrate/nitrite also increased with ischaemia but decreased after 2‐h reperfusion. Pre‐treatment with an inducible nitric oxide synthase inhibitor (1400W; Cayman Chemical Company, Ann Arbor, MI, USA) attenuated inducible nitric oxide synthase activity, reactive nitrogen species generation and pulmonary vascular resistance, but did not affect total nitrate/nitrite. Endothelial nitric oxide synthase expression was unchanged by ischaemia–reperfusion; however, its phosphorylation on serine 1177 and dephosphorylation on threonine 495 was uncoupled, suggesting decreased endothelial nitric oxide synthase activity. 1400W prevented uncoupling of endothelial nitric oxide synthase phosphorylation, maintaining its activity during reperfusion.

Conclusion:  Ischaemia–reperfusion up‐regulates inducible nitric oxide synthesis and/activity, which coincides with reduced endothelial nitric oxide synthase activity as suggested by its uncoupling and may contribute to ischaemia–reperfusion‐induced pulmonary vasoconstriction.
Evaluation of the effects by implementing and improving the ‘Flood Hazard Mapping Training Course’
Authors: Ikeda T. , Kuribayashi D. , Tanaka S.
Published: August 2011

In addition to structural measures such as flood protection levees, dams and retarding basins, flood hazard maps (hereafter referred to as ‘FHMaps’), as a part of nonstructural measures, has recently been recognized as more important in Japan, which has suffered from recurrent flood disasters until today. By utilizing the experience of training on flood management, Japan International Cooperation Agency and the International Centre for Water Hazard and Risk Management implemented the ‘Flood Hazard Mapping Training Course’ (hereafter referred to as ‘FHM‐TC’) for 5 years from FY2004. The FHM‐TC was implemented successfully by improving the framework and curriculum of the training course and by reflecting comments and requests from trainees of the past training courses who participated in the follow‐up activities. This paper introduces the outline of FHM‐TC, which includes the recently developed field exercise method ‘Town‐watching’, and it describes the year‐by‐year improvement of the FHM‐TC from its implementation of the previous years (e.g. the enhancement of the management and support systems), and the development of supporting tools based on the feedbacks of the follow‐up seminars. It also evaluates the effect of the training course on the trainees' understanding level on flood hazard mapping, which was investigated by conducting questionnaire survey and giving simple test to the trainees. Furthermore, it presents the development of a new training course by utilizing the experiences of the FHM‐TC.
“Es kehrt niemand heil zu seinem Gott zurück—”: Biblical Archetypes as Representational Devices in the Poetry of Nelly Sachs
Authors: Martin Elaine
Published: August 2011

No restitution for Job, no last‐minute divine intervention: Nelly Sachs's refusal to impose any kind of redemptive framework on the suffering of the Holocaust is the subject of this article. Her use of Biblical archetypes can be considered a highly significant representational device in her œuvre since, contrary to the claims made in much existing Sachs scholarship, they serve as an effective means of refuting any redemptive or religious, “sense‐making” framework for the horrors of Auschwitz. This is significant given the frequent references to Sachs as a supposedly “redemptive poet,” a gravely erroneous claim that has found many willing proponents in critical discourse, to the detriment of what is in fact an absolute denunciation of any such rationalizing schema.
Choreographing Exile: Lothar Warneke's and Omar Saavedra Santis's Blonder Tango
Authors: Trnka Jamie H.
Published: August 2011

Lothar Warneke's film Blonder Tango, based on exiled Chilean Omar Saavedra Santis's novel of the same title, pairs German and Chilean experiences of violence, antifascism, and exile against the backdrop of 1970s East Germany. Three aspects of the film are particularly rich points of entry into the treatment of antifascist solidarities globally, all of them underwritten by diverse practices of comparison: intermediality, translation, and rewritings of cultural and literary histories. For both the novel and the film, translative reading opens meaningful relationships among territories, conflicts, and protagonists in tandem with a contrapuntal, historical analysis. This article explores what competing assessments of the film as a project and as an artifact tell us about the kinds of cultural labor that antifascism does for different constituencies in a Chilean‐German relationship. In the process, it offers one model for rethinking the objects and methods of analysis in German Cultural Studies today.
Spatial distribution of seroprevalence forAnaplasma phagocytophilum,Borrelia burgdorferi,Ehrlichia canis, andDirofilaria immitisin dogs in Washington, Oregon, and California
Authors: Carrade Danielle , Foley Janet , Sullivan Michael , Foley Colin W. , Sykes Jane E.
Published: August 2011

Background:In the US little spatially defined information regarding exposure to most vector‐borne pathogens in dogs is available for the states of California (CA), Oregon (OR), and Washington (WA).

Objectives:The purpose of the present study was to evaluate the spatial distribution of seroprevalence for 4 vector‐borne pathogens,Anaplasma phagocytophilum,Borrelia burgdorferi,Ehrlichia canis, andDirofilaria immitis, across the 3 western coastal states of the contiguous United States that extend from the northern Mexican to the southern Canadian border.

Methods:A convenience sample, targeting blood from 20 pet dogs per county across CA, OR, and WA, was evaluated using a canine point‐of‐care ELISA kit. Geographic coordinates of home zip code were displayed using a geographic information system. A total of 2431 dogs from CA, OR, and WA were tested.

Results:The overall seroprevalence was highest forA. phagocytophilum(2.4%), followed byB. burgdorferi(1.2%), andE. canis(0.7%). The prevalence of infection withD. immitiswas 0.7%. At the individual dog level, there was a significant association between seropositivity toB. burgdorferiandA. phagocytophilum(odds ratio=18.7, 95% confidence interval=6.8–47.1). For most positive results, prevalence tended to decrease with increasing latitude; thus, the highest rates of seropositivity occurred in CA, followed by OR, and then WA; one exception was seropositivity forB. burgdorferi, which was higher in WA (0.38%) than in OR (0.15%), but considerably lower than in CA (2.00%). In WA, dogs that tested positive forA. phagocytophilum,E. canis, andB. burgdorferiwere in the southern Puget Sound area. ForD. immitis, none of the dogs in WA was positive.

Conclusions:Seropositivity for vector‐borne pathogens is broadly but patchily distributed in dogs in CA, OR, and WA.
Clinicopathologic abnormalities associated with snake envenomation in domestic animals
Authors: Goddard Amelia , Schoeman Johan P. , Leisewitz Andrew L. , Nagel Salome S. , Aroch Itamar
Published: August 2011

Abstract: Envenomation of domestic animals by snakes occurs frequently in certain geographic areas. However, reports describing clinical signs, clinicopathologic abnormalities, therapeutic approaches, and outcomes are sparse. This review summarizes various snake families, venom types associated with harmful snakes, and the significant hematologic, hemostatic, and biochemical abnormalities associated with envenomation. Hematologic abnormalities include RBC membrane abnormalities, hemolysis, hemoconcentration, leukogram changes, and platelet abnormalities, specifically thrombocytopenia. Coagulopathies associated with snake envenomation are well described in human medicine, and many studies have demonstrated properties of venoms that lead to both procoagulation and anticoagulation. As expected, similar abnormalities have been described in domestic animals. Biochemical abnormalities are associated with the effects of venom on tissues such as liver, skeletal and cardiac muscle, vascular endothelium, and kidney as well as effects on protein components and cholesterol. This comprehensive review of clinicopathologic abnormalities associated with envenomation and their relationships to characterized venom constituents should be useful both in the diagnosis and management of envenomation and should serve as a foundation for future research in this field.
Tick toxicosis in a dog bitten by Ornithodoros brasiliensis
Authors: Reck José , Soares João Fábio , Termignoni Carlos , Labruna Marcelo B. , Martins João Ricardo
Published: August 2011

Abstract: Ticks are hematophagous parasites of people and animals and are a public health hazard in several countries. They are vectors of infectious diseases; in addition, the bite of some ticks, mainly from the Ornithodoros genus, may lead to local lesions and systemic illness, referred to as tick toxicosis. In this report, we describe a dog bitten by Ornithodoros brasiliensis, popularly known as the mouro tick. The main clinical findings were disseminated skin rash, pruritus, mucosal hyperemia, lethargy, and fever. Laboratory abnormalities 48 hours after the bites occurred included mild nonregenerative anemia, eosinophilia, basophilia, increased serum creatine kinase activity, increased serum C‐reactive protein concentration, and prolonged coagulation times. Tick‐borne pathogens were not detected by PCR analysis or serologic testing, supporting the diagnosis of a noninfectious syndrome due to tick bite, compatible with tick toxicosis.
Waldenström's macroglobulinemia in a dog with a bleeding diathesis
Authors: Jaillardon Laetitia , Fournel‐Fleury Corinne
Published: August 2011

Abstract: An 11‐year‐old female spayed Whippet dog was referred to the Veterinary Hospital of the National Veterinary School of Lyon with a 3‐month history of chronic bleeding, cutaneous masses suggestive of hematomas, and hemorrhagic diarrhea. Laboratory abnormalities included leukopenia with neutropenia and lymphopenia, rouleaux formation, marked hyperproteinemia with hyperglobulinemia and normoalbuminemia, hypercalcemia, markedly increased serum urea concentration, mildly increased creatinine concentration, and proteinuria. Hemostatic screening tests showed marked prolongation of thrombin time, increased concentrations of fibrin(ogen) degradation products and D‐dimers, and slightly prolonged activated partial thromboplastin time. Serum and urine protein electrophoresis revealed a monoclonal peak identified as IgM by immunoelectrophoresis and an M‐spike, respectively. Cytologic evaluation of bone marrow revealed a hypocellular sample with lymphoplasmacytic cells comprising approximately 50% of all nucleated cells. These findings were consistent with a diagnosis of Waldenström's macroglobulinemia with secondary bleeding diathesis. Treatment with prednisone and chlorambucil was initiated, and the dog had a good response.
Alternative therapeutic advantages of catfish bile on atopic dermatitis: protection of T cell-mediated skin disease via antioxidant activities
Authors: Lee Do Ik , Huh Yoon Joo , Hwang Kwang Woo , Choi YoungWook , Choi Jae-Seok , Han Sam-Yong , Gyoung Young-Soo , Joo Seong Soo
Published: August 2011

Objectives

In the present study, we aimed to examine the anti-atopic properties of bile from the cat fish, Silurus asotus, to determine its possible use as a pharmaceutical product.

Methods

The anti-atopic activities of cat fish bile were examined in a non-cell antioxidant, in-vitro assay (splenocytes and mast cells) and a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like mouse model.

Results

The results of these experiments revealed that Silurus asotus bile (SAB) scavenges radicals and protects proteins from superoxide attacks, suggesting that SAB suppresses the T helper (Th) type 2-skewed immune response. Th1/Th2 mRNA cytokines (interleukin (IL)-2, interferon (IFN)-γ and IL-4) from mouse splenocytes were effectively inhibited, and the release of β-hexosaminidase in RBL-2H3 mast cells was significantly suppressed by SAB. These results were supported by screening the Th1/Th2 cytokine mRNAs (IL-2, IFN-γ and IL-4) from lymph nodes in DNCB-treated mice. More dramatic results were observed in the histological changes at higher SAB concentrations (5%) compared to the therapeutic control, visualized using hematoxylin–eosin (H&E) staining.

Conclusions

The results presented in this study suggest that SAB may provide functional advantages with regard to treating atopic dermatitis because of its antioxidant and immune-suppressive effects.
Bootstrap methods for comparing independent regression slopes
Authors: Ng Marie , Wilcox Rand R.
Published: August 2011

In this study, we explore the effects of non‐normality and heteroscedasticity when testing the hypothesis that the regression lines associated with multiple independent groups have the same slopes. The conventional approach involving the F‐test and the t‐test (F/t approach) is examined. In addition, we introduce two robust methods which allow simultaneous testing of regression slopes. Our results suggest that the F/t approach is extremely sensitive to violations of assumptions and tends to yield misleading conclusions. The new robust alternatives are recommended for general use.
Neuronal homeostasis: time for a change?
Authors: O’Leary Timothy , Wyllie David J. A.
Published: August 2011

Abstract  Homeostatic processes that regulate electrical activity in neurones are now an established aspect of physiology and rest on a large body of experimental evidence that points to roles in development, learning and memory, and disease. However, the concepts underlying homeostasis are too often summarized in ways that restrict their explanatory power and obviate important subtleties. Here, we present a review of the underlying theory of homeostasis – control theory – in an attempt to reconcile some existing conceptual problems in the context of neuronal physiology. In addition to clarifying the underlying theory, this review highlights the remaining challenges posed when analysing homeostatic phenomena that underlie the regulation of neuronal excitability. Moreover, we suggest approaches for future experimental and computational work that will further our understanding of neuronal homeostasis and the fundamental neurophysiological functions it serves.
Calcitonin gene‐related peptide restores disrupted excitation–contraction coupling in myotubes expressing central core disease mutations in RyR1
Authors: Vega Ana Victoria , Ramos‐Mondragón Roberto , Calderón‐Rivera Aida , Zarain‐Herzberg Angel , Avila Guillermo
Published: August 2011

Non‐Technical Summary  Central core disease (CCD) is linked to mutations in the skeletal muscle ryanodine receptor (RyR1) gene that are believed to disrupt excitation–contraction (EC) coupling. EC coupling requires activation of RyR1s to release Ca2+ from the sarcoplasmic reticulum (SR). Subsequently, the SR Ca2+‐ATPase (SERCA) returns cytoplasmic Ca2+ to intracellular stores. Here, we have investigated the effects of two CCD RyR1 mutants (I4897T and Y523S) in C2C12 myotubes. Both mutations significantly altered myogenesis and SERCA gene expression – inhibition by I4897T and stimulation by Y523S. They are thought to behave differently (‘Ca2+‐impermeable’ and ‘leaky’, respectively), but disrupted EC coupling through the same mechanism (store depletion). It is conceivable that reduced SERCA expression by I4897T could explain this paradox. In both cases, the neuropeptide CGRP restored EC coupling by increasing SR Ca2+ content. We propose that CGRP and its corresponding signalling pathway exert beneficial effects in myotubes expressing CCD mutants.
Spinal direct current stimulation modulates the activity of gracile nucleus and primary somatosensory cortex in anaesthetized rats
Authors: Aguilar J. , Pulecchi F. , Dilena R. , Oliviero A. , Priori A. , Foffani G.
Published: August 2011

Non‐Technical Summary  Stimulation of the human brain with direct current is a simple but effective neuromodulation technique that is becoming increasingly popular due to its potentiality for non‐invasively treating a variety of neurological and neuropsychiatric disorders. Recently, this neuromodulation technique has been extended to the stimulation of the human spinal cord. Here we investigated the mechanisms of action of spinal direct current stimulation (sDCS) in anaesthetized rats. We found that sDCS can selectively modulate the spontaneous activity entering the brain through the spinal cord via the somatosensory system, consequently modulating both the internal state of the brain and its responsiveness to external somatosensory stimuli. These findings have at least two levels of significance: from a physiological perspective, they remark on the importance of the spinal cord in regulating the state of the brain; from a clinical perspective, they offer a mechanistic rationale for the development of sDCS as an effective bottom‐up neuromodulation technique.
Effects of ageing on single muscle fibre contractile function following short‐term immobilisation
Authors: Hvid Lars G. , Ørtenblad Niels , Aagaard Per , Kjaer Michael , Suetta Charlotte
Published: August 2011

Non‐Technical Summary  The contractile function of human single muscle fibres is of particular importance for whole muscle contractile function. Yet, whereas ageing and short‐term disuse (immobilisation) separately have been shown to impair single fibre contractile function, very little attention has been given to their combined effects. We show that 2 weeks of lower limb immobilisation reduces force and specific force (force per cross‐sectional area) of both slow and fast single muscle fibres and that this occurred to a similar extent in young and old individuals. In contrast, disuse led to reduced Ca2+ sensitivity in fast fibres of young and in slow fibres of old, respectively. These results help us to better understand the underlying physiological mechanisms responsible for the deleterious effects of short‐term disuse on whole muscle contractile function in both young and old.
Distinct mechanisms regulate GABAA receptor and gephyrin clustering at perisomatic and axo‐axonic synapses on CA1 pyramidal cells
Authors: Panzanelli Patrizia , Gunn Benjamin G. , Schlatter Monika C. , Benke Dietmar , Tyagarajan Shiva K. , Scheiffele Peter , Belelli Delia , Lambert Jeremy J. , Rudolph Uwe , Fritschy Jean‐Marc
Published: August 2011

Non‐Technical Summary  To be effective, synaptic transmission requires precise alignment of the presynaptic terminal, releasing the neurotransmitter, with the postsynaptic density, where receptors are present at high density. Complex molecular mechanisms ensure this interplay between neurons and, in addition, stabilize receptors in the postsynaptic membrane. To explore these mechanisms at GABAergic synapses, which mediate inhibitory neurotransmission in the brain, we investigated here the consequences of ‘removing’ the receptors, using targeted gene deletion. Our results show that the receptors are dispensable for synapse formation, but are required for the postsynaptic aggregation of several proteins involved in receptor trafficking, anchoring and regulation. Defects in the molecular regulation of GABAergic synapses have been associated with neurodevelopmental disorders, mental retardation, anxiety and mood disorders, underscoring the relevance of fine tuning of GABAergic inhibition for proper brain function.
Analytic Bounds for Instability Regions in Periodic Systems With Delay via Meissner’s Equation
Authors: Butcher Eric A. , Mann Brian P.
Published: August 2011

A method for obtaining analytic bounds for period doubling and cyclic fold instability regions in linear time-periodic systems with piecewise constant coefficients and time delay is suggested. The method is based on the use of transition matrices for Meissner’s equation corresponding to the desired type of instability. Analytic expressions for the disconnected regions of fold and flip instability for two- and three-segment coefficients including both complex and real eigenvalues in Meissner’s equation are obtained. The proposed method when applied to the example of two-segment interrupted turning with complex eigenvalues in each segment yields the same results as those obtained recently for the boundaries of the flip regions (Szalai and Stepan, 2006, “Lobes and Lenses in the Stability Chart of Interrupted Turning,” J Comput. Nonlinear Dyn., 1, pp. 205–211). Next, the period-doubling instability regions for a particular delay differential equation related to the damped Meissner’s equation and the fold instabilities for a model of delayed position feedback control are analytically obtained. Finally, we extend the method to a single degree-of-freedom milling model with a three-piecewise-constant-segment approximation to the true specific cutting force in which lower bounds for and horizontal locations of the regions of flip instability are obtained. The analytic results are verified through numerical stability charts obtained using the temporal finite element method. Conditions for the existence of islands of instability are also obtained.
Protein adsorption on and swelling of polyelectrolyte brushes: A simultaneous ellipsometry-quartz crystal microbalance study
Authors: Bittrich Eva , Rodenhausen Keith Brian , Eichhorn Klaus-Jochen , Hofmann Tino , Schubert Mathias , Stamm Manfred , Uhlmann Petra
Published: August 2011

With a coupled spectroscopic ellipsometry-quartz crystal microbalance with dissipation (QCM-D) experimental setup, quantitative information can be obtained about the amount of buffer components (water molecules and ions) coupled to a poly(acrylic acid) (PAA) brush surface in swelling and protein adsorption processes. PAA Guiselin brushes with more than one anchoring point per single polymer chain were prepared. For the swollen brushes a high amount of buffer was found to be coupled to the brush-solution interface in addition to the content of buffer inside the brush layer. Upon adsorption of bovine serum albumin the further incorporation of buffer molecules into the protein-brush layer was monitored at overall electrostatic attractive conditions [below the protein isolectric poimt (IEP)] and electrostatic repulsive conditions (above the protein IEP), and the shear viscosity of the combined polymer-protein layer was evaluated from QCM-D data. For adsorption at the “wrong side” of the IEP an incorporation of excess buffer molecules was observed, indicating an adjustment of charges in the combined polymer-protein layer. Desorption of protein at pH 7.6 led to a very high stretching of the polymer-protein layer with additional incorporation of high amounts of buffer, reflecting the increase of negative charges on the protein molecules at this elevated pH.
Impact of parasitic reactions on wafer-scale uniformity in water-based and ozone-based atomic layer deposition
Authors: Henn-Lecordier Laurent , Anderle Mariano , Robertson Erin , Rubloff Gary W.
Published: August 2011

The exceptional thickness control and conformality of atomic layer deposition (ALD) has made it the process of choice for numerous applications from microelectronics to nanotechnology. Its benefits derive from the self-limiting character of surface chemical processes (adsorption and chemical reaction) that occur upon saturation of the active sites present on the surface. However, identifying a suitable process window in which ALD benefits are realized at the wafer scale can be a challenge, even in favorable cases. The authors explore here the prototypical case of ALD Al2O3 obtained from trimethyl aluminum (TMA), using a cross-flow ALD reactor design chosen to highlight deviations from expectations for true ALD behavior. Cross-wafer uniformity at the wafer scale (100 mm diameter) is investigated for both water and ozone used as oxidants, as a function of precursor dose and nitrogen purge conditions outside as well as inside the parameter space where ALD’s process benefits are realized. While nonuniformities lower than 1% were achievable for both oxidants, the ozone-based process offers significant benefits over the water-based process, namely, a broader process window and 3 × lower TMA dosages. The growth per cycle and uniformity are essentially unchanged with overexposures of either TMA or ozone. However, for overdosing of water growth rates are considerably higher than the nominal 0.95 Å/cycle and as well as degraded uniformity are observed. While underdosing of all precursor results in depletion of film growth in the flow direction across the wafer surface, these nonuniformities are more dramatic for water than ozone. These observations suggest the use of water as oxidant, if in excess dose condition, can introduce parasitic reactions in addition to the fundamental half-reactions for ALD Al2O3. Such reactions, e.g., associated with excess hydrogen-bonded water, lead to enhanced growth rates and degradation of uniformity.
Inductively coupled plasma etching of graded-refractive-index layers of TiO2 and SiO2 using an ITO hard mask
Authors: Noemaun Ahmed N. , Mont Frank W. , Cho Jaehee , Schubert E. Fred , Kim Gi Bum , Sone Cheolsoo
Published: August 2011

Transparent dielectric layers with varying compositions of TiO2 and SiO2, and ITO are deposited on sapphire and Si substrates by using an RF sputter system. Inductively coupled plasma (ICP) reactive ion etching (RIE) of the ITO hard mask is examined under H2, CH4, and Cl2 chemical environments. The slope of the sidewall and the etch residue on the sidewall of the ITO hard mask are controlled by the flow rates of H2, CH4, and Cl2. ICP-RIE dry etch of TiO2 and SiO2 is investigated under fluorinated environments. Comparable etch rates of TiO2 and SiO2 (ratio ≈ 2:1) and high selectivity ≫ 1 over ITO are found. Graded-refractive-index (GRIN) layers, made up of multiple dielectric layers of TiO2 and SiO2, are patterned to form cylindrical pillars by ICP etching using the ITO hard mask. Fluorine containing residues are identified on the TiO2 and SiO2 surfaces. Various etch chemistries are investigated to obtain smooth, vertical, and residue-free sidewalls of the GRIN pillars.
Improved motion‐compensated image reconstruction for PET using sensitivity correction per respiratory gate and an approximate tube‐of‐response backprojector
Authors: Dikaios Nikolaos , Fryer Tim D
Published: August 2011

Purpose:

One limitation of positron emission tomography (PET) imaging of the torso is patient motion. Motion‐compensated image reconstruction (MCIR) is one method employed to reduce the deleterious effects of motion. Existing MCIR algorithms use a single sensitivity correction term, which provides inexact normalization for multigate data. Consequently, in this study, the authors derive and examine the performance of an MCIR algorithm with sensitivity correction per gate. In addition, they demonstrate an approximate tube‐of‐response (TOR) backprojector.

Methods:

Simulated data from the NCAT phantom with six lesions added were used to compare MCIR algorithms with and without the incorporation of sensitivity correction per gate and TOR backprojection to postreconstruction registration (PRR) and images reconstructed without motion correction. To make the simulations more realistic, intragate motion was included. Deformation fields were determined from NCAT anatomical images using a free‐form deformation approach with bending energy regularization.

Results:

Sensitivity correction per gate and TOR backprojection improved mean lesion contrast‐to‐noise ratio by 6%–8%, with the maximum increase (21%–23%) found for the smallest lesion. These increases were obtained despite a small increase (3%) in noise as measured by standard deviation in a uniform lung region. Sensitivity correction per gate comes at no extra computational cost, whilst replacing line‐of‐response backprojection with TOR backprojection increased the overall computation time by ∼20%. In addition, MCIR was found to be superior to PRR, with one factor contributing to this difference being the differential impact of interpolation following deformation. MCIR was also shown to exhibit super‐resolution.

Conclusions:

Replacing a single sensitivity correction term in MCIR with sensitivity correction per gate improves lesion detectability. For a small increase in computational expense, further improvements are achieved using an approximate TOR backprojector rather than line‐of‐response backprojection.
Bridging the gap between IMRT and VMAT: Dense angularly sampled and sparse intensity modulated radiation therapy
Authors: Li Ruijiang , Xing Lei
Published: August 2011

Purpose:

To propose an alternative radiation therapy (RT) planning and delivery scheme with optimal angular beam sampling and intrabeam modulation for improved dose distribution while maintaining high delivery efficiency.

Methods:

In the proposed approach, coined as dense angularly sampled and sparse intensity modulated RT (DASSIM‐RT), a large number of beam angles are used to increase the angular sampling, leading to potentially more conformal dose distributions as compared to conventional IMRT. At the same time, intensity modulation of the incident beams is simplified to eliminate the dispensable segments, compensating the increase in delivery time caused by the increased number of beams and facilitating the plan delivery. In a sense, the proposed approach shifts and transforms, in an optimal fashion, some of the beam segments in conventional IMRT to the added beams. For newly available digital accelerators, the DASSIM‐RT delivery can be made very efficient by concatenating the beams so that they can be delivered sequentially without operator's intervention. Different from VMAT, the level of intensity modulation in DASSIS‐RT is field specific and optimized to meet the need of each beam direction. Three clinical cases (a head and neck (HN) case, a pancreas case, and a lung case) are used to evaluate the proposed RT scheme. DASSIM‐RT, VMAT, and conventional IMRT plans are compared quantitatively in terms of the conformality index (CI) and delivery efficiency.

Results:

Plan quality improves generally with the number and intensity modulation of the incident beams. For a fixed number of beams or fixed level of intensity modulation, the improvement saturates after the intensity modulation or number of beams reaches to a certain level. An interplay between the two variables is observed and the saturation point depends on the values of both variables. For all the cases studied here, the CI of DASSIM‐RT with 15 beams and 5 intensity levels (0.90, 0.79, and 0.84 for the HN, pancreas, and lung cases, respectively) is similar with that of conventional IMRT with seven beams and ten intensity levels (0.88, 0.79, and 0.83) and is higher than that of single‐arc VMAT (0.75, 0.75, and 0.82). It is also found that the DASSIM‐RT plans generally have better sparing of organs‐at‐risk than IMRT plans. It is estimated that the dose delivery time of DASSIM‐RT with 15 beams and 5 intensity levels is about 4.5, 4.4, and 4.2 min for the HN, pancreas, and lung case, respectively, similar to that of IMRT plans with 7 beams and 10 intensity levels.Conclusion: DASSIS‐RT bridges the gap between IMRT and VMAT and allows optimal sampling of angular space and intrabeam modulation, thus it provides improved conformity in dose distributions while maintaining high delivery efficiency.
Distinct Phosphorylation Sites on the β
2
-Adrenergic Receptor Establish a Barcode That Encodes Differential Functions of β-Arrestin
Authors: Nobles Kelly N. , Xiao Kunhong , Ahn Seungkirl , Shukla Arun K. , Lam Christopher M. , Rajagopal Sudarshan , Strachan Ryan T. , Huang Teng-Yi , Bressler Erin A. , Hara Makoto R. , Shenoy Sudha K. , Gygi Steven P. , Lefkowitz Robert J.
Published: August 2011

Different patterns of GPCR phosphorylation produce distinct conformations of β-arrestin and specific downstream responses.
Quantitative Encoding of the Effect of a Partial Agonist on Individual Opioid Receptors by Multisite Phosphorylation and Threshold Detection
Authors: Lau Elaine K. , Trester-Zedlitz Michelle , Trinidad Jonathan C. , Kotowski Sarah J. , Krutchinsky Andrew N. , Burlingame Alma L. , von Zastrow Mark
Published: August 2011

Partial and full agonists of opioid receptors produce distinct responses by enriching distinct populations of phosphorylated receptors.
Science Signaling
Podcast: 9 August 2011
Authors: von Zastrow Mark , VanHook Annalisa M.
Published: August 2011

Opioid receptors stimulated with morphine signal less efficiently than those stimulated with an endogenous opioid peptide.
Focus Issue: Cracking the G Protein–Coupled Receptor Code
Authors: Gough Nancy R.
Published: August 2011

Signaling by GPCRs is encoded and decoded to produce ligand-specific, cell-specific, and genome-specific responses.
Spare the Brain
Authors: Wong Wei
Published: August 2011

Anaplastic lymphoma kinase ensures continued signaling through growth-promoting pathways in the fly CNS during nutrient deprivation.
Getting to the Heart of the Matter
Authors: Thompson Heather M.
Published: August 2011

Polarized cell protrusions promote localized induction of heart progenitor cells.
Development’s a No-Go Without a Nogo Antagonist
Authors: Ray L. Bryan
Published: August 2011

A molecule that functions in normal olfactory tract development could provide clues to failed neuronal regeneration in adults.