bluuebunny/crossref_metadata_2025 huggingface dataset:
Getting Asia Right and Advancing the Field of IR
Authors: Eun Yong-Soo , Pieczara Kamila
Published: December 2012

Why, we have to ask, have putatively inadequate ‘Western’ IR theories been applied over and over again to explain and understand Asian international relations? How can we develop more satisfying explanations of the international politics of Asia? In relation to such questions, this article demonstrates how academic disciplinary socialisation entails competition and selection, which tends towards the elimination of approaches or explanations that do not fit into the socialised practice, without generating new ones. It is argued here that interweaving existing IR theories with Asia's empirical material and remoulding the theories through gathering empirical evidence on the regional reality and converting it into theoretical variables, comparable in the field of IR, should be our goal. In order to apprehend Asian international relations better and to contribute to advancing the discipline of IR, we need an accumulation of theoretical knowledge sensitive to and attentive to local difference.
Characterization of stress response in human retinal epithelial cells
Authors: Giansanti Vincenzo , Villalpando Rodriguez Gloria E. , Savoldelli Michelle , Gioia Roberta , Forlino Antonella , Mazzini Giuliano , Pennati Marzia , Zaffaroni Nadia , Scovassi Anna Ivana , Torriglia Alicia
Published: December 2012

The pathogenesis of age‐related macular degeneration (AMD) involves demise of the retinal pigment epithelium and death of photoreceptors. In this article, we investigated the response of human adult retinal pigmented epithelial (ARPE‐19) cells to 5‐(N,N‐hexamethylene)amiloride (HMA), an inhibitor of Na+/H+ exchangers. We observed that ARPE‐19 cells treated with HMA are unable to activate ‘classical’ apoptosis but they succeed to activate autophagy. In the first 2 hrs of HMA exposure, autophagy is efficient in protecting cells from death. Thereafter, autophagy is impaired, as indicated by p62 accumulation, and this protective mechanism becomes the executioner of cell death. This switch in autophagy property as a function of time for a single stimulus is here shown for the first time. The activation of autophagy was observed, at a lesser extent, with etoposide, suggesting that this event might be a general response of ARPE cells to stress and the most important pathway involved in cell resistance to adverse conditions and toxic stimuli.
Nocturnal Penile Erections: The Role of RigiScan in the Diagnosis of Vascular Erectile Dysfunction
Authors: Elhanbly Samir , Elkholy Ayman
Published: December 2012

Introduction

To determine the etiology of cases with organic erectile dysfunction (ED), invasive techniques are needed that can induce patient anxiety and disturb test results.

Aim

To find any special patterns of nocturnal penile tumescence and rigidity (NPTR) records in cases of vasculogenic impotence that can differentiate cases of arterial and venous origin without resorting to the more invasive diagnostic tests.

Methods

This study included 95 cases of ED (77 cases with abnormal NPTR records plus 18 cases with normal NPTR). History taking and clinical examination with estimation of serum androgen hormones and postprandial blood glucose were done. All patients were then subjected to the following: NPTR monitoring using RigiScan device (Dacomed Corporation, Minneapolis, MN, USA), pharmacopenile duplex ultrasound examination, and redosing pharmacocavernosometry. According to the results of these tests, patients were classified into four groups: psychogenic, arteriogenic, venogenic, and combined arteriogenic–venogenic ED groups. Receiver operator characteristic (ROC) curve analysis of the different RigiScan parameters of venogenic group vs. the arteriogenic group was done. Best parameters were then retested by using them in prediction of veno-occlusive dysfunction (VOD) in all studied patients.

Main Outcome Measures

Different RigiScan parameters: number of events, duration of best episode, base tumescence, base rigidity, tip tumescence, and tip rigidity.

Results

RigiScan parameters were statistically lower in venogenic than in arteriogenic group and were more correlated with flow to maintain than the peak systolic velocity. ROC curve analysis showed that VOD can be predicted if the duration of the best event is <11.5 minutes (diagnostic accuracy 83.7%) or tip rigidity is <36.5% (diagnostic accuracy 81.6%). On generalizing these values in all patients, duration of best event showed diagnostic accuracy of 88.4%.

Conclusion

VOD can be predicted if duration of the best event of NPTR monitoring is less than 11.5 minutes, but the presence of concomitant arterial dysfunction cannot be excluded.
The Influence of Bolus to Infusion Delays on Plasma Tissue Plasminogen Activator Levels
Authors: Smith Curtis , Al-Nuaimi Yusur , Wainwright Jane , Sherrington Charles , Singh Arun , Kallingal Jouher , Douglass Christopher , Parry-Jones Adrian , Smith Craig , Dixit Anand , Majid Arshad
Published: December 2012

Background

Estimates of neuronal loss in acute ischemic stroke show that the typical patient may lose 1·9 million neurons each minute that treatment is delayed. Consequently, significant emphasis has been placed on early evaluation and thrombolysis with tissue plasminogen activator (TPA), the only approved thrombolytic therapy. TPA should be administered as a bolus followed by an immediate infusion because of its short half life. However, in the real life clinical situation, delays in starting the infusion after the bolus can occur. Similarly, once infusion has started, interruptions in the infusion of TPA can also occur. These scenarios may result in lower serum concentrations which could decrease the effectiveness of thrombolysis. We sought to simulate, the influence of bolus infusion delays and also the influence of different intervals of interruptions in the infusion of TPA on serum TPA concentrations.

Methods

We simulated the effect of multiple intervals of delay after the bolus on serum TPA concentrations using known pharmacokinetics parameters of TPA. The effect of different intervals of interruptions in the infusion of TPA was also determined. The effect of rebolusing with TPA on serum concentrations in the event of significant bolus to infusion delays or significant infusion interruption was also simulated.

Results

Our data show that delays in starting the infusion may have significant effects on serum TPA concentrations. After the initial bolus, there is a rapid decrease in serum TPA concentrations unless the infusion is started immediately. Greater than 5 min delays in starting the infusion results in a slow gradual increase in serum TPA levels and levels stay well below the target concentrations for significant periods of time. Similarly, interruptions in the infusion of TPA lasting longer than 5 min can also significantly influence TPA levels. Rebolusing with TPA in these scenarios rapidly restores TPA levels to target concentrations.

Conclusion

Because of its short half life, TPA should be administered as a bolus followed by an immediate infusion. Bolus to infusion delays or interruptions in the infusion of TPA after the bolus may significantly impact serum TPA levels and may reduce the efficacy of thrombolysis. Protocols or administration regimens should be employed to prevent delays or interruptions in the infusion. When delays do occur, rebolusing of TPA may be needed to rapidly restore TPA to target levels.
Transferrin Saturation and Hospital Length of Stay and Mortality in Medicare Beneficiaries
Authors: Mainous Arch G. , Diaz Vanessa A. , Knoll Michele E. , Hulihan Mary M. , Grant Althea M. , Wright Robert U.
Published: December 2012

Objectives

To evaluate in a large, nationally representative cohort the association between high serum transferrin saturation (TS) and hospital length of stay and mortality in older adults.

Design

Prospective cohort.

Setting

Longitudinal analyses of the Third National Health and Nutrition Examination Survey linked to Medicare claims from 1991 through 2006.

Participants

Medicare beneficiaries aged 65 and older at baseline.

Measurements

Transferrin saturation collected on each participant at baseline was characterized as <20.0%, 20.0% to 54.9%, and 55.0% and greater. Length of stay in the hospital and death in the hospital were primary outcomes. Analyses were adjusted for age, sex, race and ethnicity, education, and severity of illness.

Results

Individuals hospitalized during the study period (79.4%) with high (odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.05–6.12) or low (OR = 1.31, 95% CI = 1.07–1.62) TS had a significantly greater risk of death than those with moderate TS. Individuals with high TS had longer average length of stay per hospitalization (11.1 days, (standard error, SE 1.7 days), P = .01) than those with moderate TS (8.4 (0.3) days). Individuals with high TS also had more hospital days per year (8.6 (2.0) days, P = .04) than those with moderate TS (6.7 (0.5) days).

Conclusion

High TS is associated with longer length of stay and death in the hospital (unweighted N = 3,847, weighted N = 28,395,464).
Smoking as a risk factor for oral candidiasis in HIV‐infected adults
Authors: Chattopadhyay Amit , Patton Lauren L
Published: December 2012

Objective

We aimed to examine if smoking is an independent predictor of oral candidiasis (OC) among HIV‐1 infected persons.

Methods

The cross‐sectional part of this study evaluated 631 adult dentate HIV‐1 seropositive persons examined for OC from 1995–2000 at the University of North Carolina Hospitals in Chapel Hill, NC. In the second part, from the above sample, a total of 283 individuals who were free of HIV‐associated oral diseases at baseline were followed up for 2 years to assess incident OC events. Data collected from medical record review, interview questionnaires, and clinical examinations were analyzed using chi‐squared tests and t‐tests. Logistic regression models were developed for prevalent OC employing the likelihood ratio test, whereas Poisson regression models were developed for assessing cumulative incidence of OC. These models included a variety of independent variables to adjust for confounding.

Results

Thirteen percent of participants had OC only; 4.6% had OC with Oral Hairy Leukoplakia; and 69.7% had neither. Smoking was associated with OC in all models [prevalent OC – current smokers: logistic regression – Odd ratio (95% CI) = 2.5 (1.3, 4.8); Incident OC – current smokers: Poisson regression (main effects model) – Incidence rate ratio (95% CI) = 1.9 (1.1, 3.8)]. Other Poisson regression models suggested evidence for effect modification between CD4 cell count and incident OC by smoking.

Conclusion

Smoking is an independent risk factor for the development of OC in HIV‐1 infected persons, and the risk of OC is modified by CD4 cell count which measures strength of the immune system.
Feeding untreated and pasteurized waste milk and bulk milk to calves: effects on calf performance, health status and antibiotic resistance of faecal bacteria
Authors: Aust V. , Knappstein K. , Kunz H.‐J. , Kaspar H. , Wallmann J. , Kaske M.
Published: December 2012

Non‐saleable milk (waste milk, WM) is contaminated with an undefined spectrum of potentially harmful pathogens and antimicrobial residues. The objective of this study was to determine the impact of feeding bulk milk (BM) or WM – both pasteurized or not – on calf performance, health and the antibiotic resistance of specific faecal bacteria. A total of 114 calves from a large‐scale dairy were housed outdoors in individual hutches and were randomly assigned to one of four feeding groups. The calves were fed either WM, pasteurized WM (pWM), BM or pasteurized BM (pBM) from day 3 to 56 of life. Milk samples taken from the pasteurizer and calves’ nipple buckets were investigated at regular intervals for total plate count and counts of thermoduric bacteria, coliforms and mastitis pathogens. Faecal samples were taken on days 2, 14, 28 and 56 of life from randomly selected calves of the WM, pWM and BM groups (eachN = 8–9) and processed to obtain from each sample preferably two isolates ofEscherichia (E.) coliandEnterococcusspp. respectively. Isolates were tested for their antimicrobial susceptibility to 25 antimicrobial agents by broth microdilution. Daily weight gain, milk and calf starter intake and health parameters did not differ significantly between the calves of the four feeding groups. The proportion of resistantE. coliisolates was significantly higher in calves fed WM and in calves fed pWM (most pronounced for cephalosporins) than in calves receiving BM. No differences in resistance were found forEnterococusspp. Thus, the concerns for selecting resistant faecal bacteria by feeding WM seem to be justified. Nonetheless, pasteurized WM of cows not treated with antimicrobials represents an acceptable feed for young calves.
Structure and diversity of intertidal benthic diatom assemblages in contrasting shores: a case study from the Tagus estuary1
Authors: Ribeiro Lourenço , Brotas Vanda , Rincé Yves , Jesus Bruno
Published: December 2012

The structure of intertidal benthic diatoms assemblages in the Tagus estuary was investigated during a 2‐year survey, carried out in six stations with different sediment texture. Nonparametric multivariate analyses were used to characterize spatial and temporal patterns of the assemblages and to link them to the measured environmental variables. In addition, diversity and other features related to community physiognomy, such as size‐class or life‐form distributions, were used to describe the diatom assemblages. A total of 183 diatom taxa were identified during cell counts and their biovolume was determined. Differences between stations (analysis of similarity (ANOSIM), R = 0.932) were more evident than temporal patterns (R = 0.308) and mud content alone was the environmental variable most correlated to the biotic data (BEST, ρ = 0.863). Mudflat stations were typically colonized by low diversity diatom assemblages (H′ ~ 1.9), mainly composed of medium‐sized motile epipelic species (250–1,000 μm3), that showed species‐specific seasonal blooms (e.g., Navicula gregaria Donkin). Sandy stations had more complex and diverse diatom assemblages (H′ ~ 3.2). They were mostly composed by a large set of minute epipsammic species (<250 μm3) that, generally, did not show temporal patterns. The structure of intertidal diatom assemblages was largely defined by the interplay between epipelon and epipsammon, and its diversity was explained within the framework of the Intermediate Disturbance Hypothesis. However, the spatial distribution of epipelic and epipsammic life‐forms showed that the definition of both functional groups should not be over‐simplified.
Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome
Authors: Vroegop Anneclaire V. M. T. , Vanderveken Olivier M. , Dieltjens Marijke , Wouters Kristien , Saldien Vera , Braem Marc J. , Van de heyning Paul H.
Published: December 2012

The aim of this study was to assess the value of drug‐induced sleep endoscopy (DISE) using a custom‐made simulation bite in maximal comfortable protrusion (MCP) of the mandible, in the prediction of treatment outcome for obstructive sleep apnea (OSA) with a mandibular advancement device (MAD). Two hundred patients (74% male; age 46 ± 9 years; apnea–hypopnea index [AHI] 19 ± 13 h−1 sleep; body mass index [BMI] 27 ± 4 kg m−2) with sleep‐disordered breathing underwent DISE with a simulation bite in MCP. One hundred and thirty‐five patients with an established diagnosis of OSA commenced MAD treatment. The associations between the findings during DISE with simulation bite and treatment outcome were evaluated. Treatment response was defined as a reduction in AHI following MAD treatment of ≥ 50% compared to baseline. Overall MAD treatment response in the studied population was 69%. The results of this study demonstrated a statistically significant association between a positive effect of the simulation bite on the upper airway patency during DISE and treatment response with MAD (P < 0.01). The results of this study suggest that the use of a simulation bite in maximal comfortable protrusion (MCP) of the mandible, as used during DISE in patients with OSA, tends to be effective in predicting treatment response of MAD treatment.
Striving for general validity: a huge sample reveals faint traces in forests
Authors: Wildi Otto
Published: December 2012

Species composition in forest patches is influenced by distance‐to‐edge within an average range of 748 m. Pellissier et al., in this issue, assess the significance of this pattern using a very large data set, a well‐defined target population and comprehensive logistic models. This is a recipe for overcoming the lack of general validity frequently observed in vegetation science.
Embodied empathy‐in‐action: overweight nurses’ experiences of their interactions with overweight patients
Authors: Aranda Kay , McGreevy Debbie
Published: December 2012

Obesity is now commonly recognised to be a significant public health issue worldwide with its increasing prevalence frequently described as a global epidemic. In the United Kingdom, primary care nurses are responsible for weight management through the provision of healthy eating advice and support with lifestyle change. However, nurses themselves are not immune to the persistent and pervasive global levels of weight gain. Drawing on a Gadamerian informed phenomenological study of female primary care nurses in England, this paper considers the complex gendered understandings and experiences of being overweight, and of food and eating. The nurses’ emotional and injurious experiences of being large is found to be capable of producing embodied caring practices, involving a fusion of horizons with patients over how it feels to inhabit a large body. Yet, even though subjected to similar derogatory stereotypes as patients, they simultaneously reinforce the dominant and damaging individualising psychopathology inherent to anti‐obesity discourses. This suggests an urgent need to expose and challenge harmful discourses surrounding women’s body size and weight in order to avoid nursing practices that unthinkingly reproduce culturally dominant and gendered understandings of weight, body size, food and eating.
Plant community type and small‐scale disturbances, but not altitude, influence the invasibility in subarctic ecosystems
Authors: Milbau Ann , Shevtsova Anna , Osler Nora , Mooshammer Maria , Graae Bente J.
Published: December 2012

Little of our knowledge about invasibility comes from arctic and alpine ecosystems, despite increasing plant migration and invasion in those regions. Here, we examine how community type, altitude, and small‐scale disturbances affect invasibility in a subarctic ecosystem.

Over a period of 4 yr, we studied seedling emergence and establishment in 17 species sown in gaps or undisturbed vegetation in four subarctic community types (Salix scrub, meadow, rich heath, poor heath) along an elevation gradient.

Invasibility was lowest in rich heath and highest in Salix scrub. Small disturbances significantly increased the invasibility in most communities, thereby showing the importance of biotic resistance to invasion in subarctic regions. Unexpectedly, invasibility did not decrease with increasing elevation, and it was also not related to summer temperature.

Our data suggest that biotic resistance might be more important than abiotic stress for invasibility in subarctic tundra and that low temperatures do not necessarily limit seedling establishment at high altitudes. High elevations are therefore potentially more vulnerable to invasion than was originally thought. Changes in community composition as a result of species migration or invasion are most likely to occur in Salix scrub and meadow, whereas Empetrum‐dominated rich heath will largely remain unchanged.
Comparison of white and red blood cell estimates in urine sediment with hemocytometer and automated counts in dogs and cats
Authors: O'Neil Elizabeth , Burton Shelley , Horney Barbara , MacKenzie Allan
Published: December 2012

Background

Therapeutic decisions regarding urinalysis are commonly based on the presence of white and red blood cells. Traditionally, numbers per high‐power field are estimated using wet‐mount microscopic examination. This technique is not standardized and counts are likely prone to inaccuracy. In addition, differentiation of leukocyte types is not possible.

Objectives

The aims of this study were to (1) compare WBC and RBC estimates using wet‐mount examination with counts obtained using a hemocytometer, (2) assess if a hematology automated analyzer (Sysmex ST‐2000iV/XT) provides reliable WBC and RBC counts in urine comparable to hemocytometer counts, and (3) evaluate air‐dried Wright–Giemsa‐stained urine drop sediment preparations for the determination of differential leukocyte counts.

Methods

WBC and RBC counts were obtained by performing wet‐mount estimates, manual hemocytometer counts, and Sysmex automated counts on 219 canine and feline urine samples. Results were correlated using Spearman rank correlation. Air‐dried Wright–Giemsa stained sediment drop preparations (n = 215) were examined for differential counts of leukocytes.

Results

A low but significant association was found between WBC estimates on wet‐mount examination and hemocytometer counts (rho = 0.37, P < .01). There was a high and significant association when RBC counts were compared between wet‐mount and hemocytometer evaluation (rho = 0.7, P < .01). There was very high and significant interassay correlation between Sysmex data from duplicate samples for what the analyzer classified as WBC (rho = 0.97, P < .01) and RBC (rho = 0.94, P < .01). Low correlations were found between the Sysmex RBC counts and both wet‐mount estimates and hemocytometer RBC counts (rho = 0.43, P < .01 and rho = 0.39, P < .01, respectively). Cell preservation in the air‐dried sediment preparations was so poor that differential counts could not be performed.

Conclusion

WBC and RBC estimates on wet‐mount examination agreed with hemocytometer counts and are therefore considered adequate. The Sysmex ST‐2000iV/XT did not provide reliable cell counts under the conditions used.
Calmodulin and calmodulin kinase II mediate emergent bursting activity in the brainstem respiratory network (preBötzinger complex)
Authors: Mironov S. L.
Published: December 2012

Key points

Rhythmic network activity can be controlled by intracellular signalling pathways but their possible role is largely not yet elucidated.

This study is focused on the mechanisms of emergence and maintenance of synchronous rhythmic activity within the preBötzinger complex (preBötC), an essential part of the respiratory network in the brainstem.

Depression of the bursting activity by brief hypoxia and electrical stimulation correlated well with ADP‐mediated inhibition of TRPM4 channels.

Long‐lasting increases in calcium during the treatments stimulated calmodulin kinase that facilitated glutamatergic synapses and augmented rhythmic activity.

The results will help us better understand how respiratory rhythm is generated and how it is restored in various respiratory disorders

Abstract  Emergence of persistent activity in networks can be controlled by intracellular signalling pathways but the mechanisms involved and their role are not yet fully explored. Using calcium imaging and patch‐clamp we examined the rhythmic activity in the preBötzinger complex (preBötC) in the lower brainstem that generates the respiratory motor output. In functionally intact acute slices brief hypoxia, electrical stimulation and activation of AMPA receptors transiently depressed bursting activity which then recovered with augmentation. The effects were abrogated after chelation of intracellular calcium, blockade of l‐type calcium channels and inhibition of calmodulin (CaM) and CaM kinase (CaMKII). Rhythmic calcium transients and synaptic drive currents in preBötC neurons in the organotypic slices showed similar CaM‐ and CaMKII‐dependent responses. The stimuli increased the amplitude of spontaneous and miniature excitatory synaptic currents indicating postsynaptic changes at glutamatergic synapses. In the acute and organotypic slices, CaM stimulated and ADP inhibited calcium‐dependent TRPM4 channels and CaMKII augmented synaptic drive currents. Experimental data and simulations show the role of ADP and CaMKII in the control of bursting activity and its relation to intracellular signalling. I propose that CaMKII‐mediated facilitation of glutamatergic transmission strengthens emergent synchronous activity within preBötC that is then maintained by periodic surges of calcium during the bursts. This may find implications in restoration and consolidation of autonomous activity in the respiratory disorders.
Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy
Authors: Cammarota Mario , Losi Gabriele , Chiavegato Angela , Zonta Micaela , Carmignoto Giorgio
Published: December 2012

Key points

In focal epilepsy the propagation of seizure discharges arising at restricted brain sites is opposed by feedforward inhibition. Failure of this inhibition marks focal seizure propagation to distant neurons.

The cellular source of inhibition and the mechanism of inhibition failure are, however, undefined.

Here we reveal that a subclass of GABAergic interneurons, i.e. the parvalbumin‐expressing, fast‐spiking interneurons, are a main source of the inhibitory signal that locally restrains seizures. Furthermore, a firing impairment in these interneurons, probably due to a drastic membrane depolarization, is an important event that by reducing the overall strength of local inhibition allows seizures to propagate across the cortex.

Our data suggest that modulation of fast‐spiking interneuron activity may represent a new therapeutic strategy to prevent generalization of focal epilepsies.

Abstract  In different animal models of focal epilepsy, seizure‐like ictal discharge propagation is transiently opposed by feedforward inhibition. The specific cellular source of this signal and the mechanism by which inhibition ultimately becomes ineffective are, however, undefined. We used a brain slice model to study how focal ictal discharges that were repetitively evoked from the same site, and at precise times, propagate across the cortex. We used Ca2+ imaging and simultaneous single/dual cell recordings from pyramidal neurons (PyNs) and different classes of interneurons in rodents, including G42 and GIN transgenic mice expressing the green fluorescence protein in parvalbumin (Pv)‐fast spiking (FS) and somatostatin (Som) interneurons, respectively. We found that these two classes of interneurons fired intensively shortly after ictal discharge generation at the focus. The inhibitory barrages that were recorded in PyNs occurred in coincidence with Pv‐FS, but not with Som interneuron burst discharges. Furthermore, the strength of inhibitory barrages increased or decreased in parallel with increased or decreased firing in Pv‐FS interneurons but not in Som interneurons. A firing impairment of Pv‐FS interneurons caused by a membrane depolarization was found to precede ictal discharge onset in neighbouring pyramidal neurons. This event may account for the collapse of local inhibition that allows spatially defined clusters of PyNs to be recruited into propagating ictal discharges. Our study demonstrates that Pv‐FS interneurons are a major source of the inhibitory barrages that oppose ictal discharge propagation and raises the possibility that targeting Pv‐FS interneurons represents a new therapeutic strategy to prevent the generalization of human focal seizures.
Crystal structure and epitaxial relationship of Ni4InGaAs2 films formed on InGaAs by annealing
Authors: Ivana  , Lim Foo Yong , Zhang Xingui , Zhou Qian , Pan Jisheng , Kong Eugene , Samuel Owen Man Hon , Yeo Yee-Chia
Published: December 2012

The structural, compositional, and electrical properties of epitaxial Ni4InGaAs2 (denoted as Ni-InGaAs) film formed by annealing sputtered Ni film on InGaAs were investigated. It was found that Ni-InGaAs adopts a NiAs (B8) structure with lattice parameters of a = 0.396 ± 0.002 nm and c = 0.516 ± 0.002 nm, and exhibits an epitaxial relationship with InGaAs, with orientations given by Ni-InGaAs[1¯10]//InGaAs[001] and Ni-InGaAs[110]//InGaAs[110]. The epitaxial Ni4InGaAs2 film has bulk electrical resistivity of ∼102 μΩ·cm, which increases as the film thickness scales below 10 nm. The results of this work would be useful for the development of contact metallization for high mobility InGaAs metal-oxide-semiconductor field-effect transistors.
Study of the Rifampin Monoresistance Mechanism in Mycobacterium tuberculosis
Authors: Pang Yu , Lu Jie , Wang Yufeng , Song Yuanyuan , Wang Shengfen , Zhao Yanlin
Published: December 2012

Rifampin (RIF) susceptibility is a key factor in determining the treatment effectiveness of the standardized treatment regimens. In
Mycobacterium tuberculosis
, both target gene mutation and the efflux pump play major roles in the resistance to antituberculosis drugs. By eliminating RIF-resistant strains with
rpoB
mutation, the choice of RIF-monoresistant strains may allow us to identify the RIF-specific efflux pump genes. This study explored the RIF monoresistance mechanism in
M. tuberculosis
. Data from DNA sequencing and MIC measurements revealed that specific mutations, including Ser531Leu and His526Asp in RpoB, show high-level drug resistance. Three-dimensional structure modeling provided further evidence that the affinity between RIF and RpoB mutants was in accordance with the drug resistance level of the corresponding isolates. Furthermore, transcription-level analysis among the nonmutated isolates indicated that three efflux pumps (Rv0783, Rv2936, and Rv0933) might be involved in exporting RIF from the cell. Compared to 8 μg/ml for wild-type
Escherichia coli
, the MICs for the transgenic
E. coli
strains with either Rv0783 or Rv2936 were 32 and 16 μg/ml, respectively. In conclusion, our study indicated that several RpoB mutant types, including Ser531Leu and His526Asp, show high-level RIF resistance attributed to low affinity between RpoB mutant proteins and RIF. In addition, this work demonstrates that Rv2936 and Rv0783 may be responsible for low-level resistance to RIF by exporting RIF from cells. The predicted structure of RpoB and the newly identified efflux pumps in this study will provide a novel approach to design new drugs and develop novel diagnosis technologies.
Assessing the Essentiality of Leishmania donovani Nitroreductase and Its Role in Nitro Drug Activation
Authors: Wyllie Susan , Patterson Stephen , Fairlamb Alan H.
Published: December 2012

The nitroimidazole fexinidazole has potential as a safe and effective oral drug therapy for the treatment of visceral leishmaniasis. To date, nitroheterocyclics have not been used in the treatment of leishmaniasis, and relatively little is known about their mechanism of action. In African trypanosomes, nitro drugs are reductively activated by a type I nitroreductase (NTR), absent in mammalian cells. Modulation of nitroreductase levels in
Trypanosoma brucei
directly affected sensitivity to nitro compounds, with reduced concentrations of the enzyme leading to moderate nitro drug resistance. In view of the progression of fexinidazole into clinical development for visceral leishmaniasis, here we assess the essentiality of the nitroreductase in
Leishmania donovani
and the effect of modulating nitroreductase levels on susceptibility to fexinidazole. The failure to directly replace both endogenous copies of the
NTR
gene, except in the presence of an ectopic copy of the gene, suggests that the
NTR
gene is essential for the growth and survival of
L. donovani
promastigotes. Loss of a single chromosomal copy of the
L. donovani NTR
gene resulted in parasites that were mildly resistant (<2-fold) to the predominant
in vivo
metabolite of fexinidazole, while parasites overexpressing NTR were 18-fold more susceptible. These data confirm that
Leishmania
NTR plays a pivotal role in fexinidazole activation. Reliance on a single enzyme for prodrug activation may leave fexinidazole vulnerable to the emergence of drug resistance. However, the essentiality of the NTR in
L. donovani
promastigotes, combined with the limited resistance shown by
NTR
single knockout cells, suggests that the potential for the spread of NTR-based resistance to fexinidazole may be limited.
Milbemycins: More than Efflux Inhibitors for Fungal Pathogens
Authors: Silva Luis Vale , Sanguinetti Maurizio , Vandeputte Patrick , Torelli Riccardo , Rochat Bertrand , Sanglard Dominique
Published: December 2012

Existing antifungal agents are still confronted to activities limited to specific fungal species and to the development of resistance. Several improvements are possible either by tackling and overcoming resistance or exacerbating the activity of existing antifungal agents. InCandida glabrata, azole resistance is almost exclusively mediated by ABC transporters (includingC. glabrata CDR1[CgCDR1] andCgCDR2) via gain-of-function mutations in the transcriptional activatorCgPDR1or by mitochondrial dysfunctions. We also observed that azole resistance was correlating with increasing virulence and fitness ofC. glabratain animal models of infection. This observation motivated the re-exploitation of ABC transporter inhibitors as a possible therapeutic intervention to decrease not only the development of azole resistance but also to interfere with the virulence ofC. glabrata. Milbemycins are known ABC transporter inhibitors, and here we used commercially available milbemycin A3/A4 oxim derivatives to verify this effect. As expected, the derivatives were inhibitingC. glabrataefflux with the highest activity for A3 oxim below 1 μg/ml. More surprising was that oxim derivatives had intrinsic fungicidal activity above 3.2 μg/ml, thus highlighting effects additional to the efflux inhibition. Similar values were obtained withC. albicans. Our data show that the fungicidal activity could be related to reactive oxygen species formation in these species. Transcriptional analysis performed both inC. glabrataandC. albicansexposed to A3 oxim highlighted a core of commonly regulated genes involved in stress responses, including genes involved in oxidoreductive processes, protein ubiquitination, and vesicle trafficking, as well as mitogen-activated protein kinases. However, the transcript profiles contained also species-specific signatures. Following these observations, experimental treatments of invasive infections were performed in mice treated with the commercial A3/A4 oxim preparation alone or in combination with fluconazole. Tissue burden analysis revealed that oxims on their own were able to decrease fungal burdens in bothCandidaspecies. In azole-resistant isolates, oxims acted synergisticallyin vivowith fluconazole to reduce fungal burden to levels of azole-susceptible isolates. In conclusion, we show here the potential of milbemycins not only as drug efflux inhibitors but also as effective fungal growth inhibitors inC. glabrataandC. albicans.
HIV-1 Dynamics and Coreceptor Usage in Maraviroc-Treated Patients with Ongoing Replication
Authors: Recordon-Pinson P. , Raymond S. , Bellecave P. , Marcelin A. G. , Soulie C. , Descamps D. , Calvez V. , Harrigan P. R. , Fleury H. , Izopet J. , Masquelier B.
Published: December 2012

There is evidence that HIV-1 evolution under maraviroc (MVC) pressure can lead to the selection of either X4-tropic variants and/or R5-tropic, MVC-resistant isolates. However, the viral dynamics of HIV-1 variants in patients with virological failure (VF) on MVC-containing regimens remain poorly studied. Here, we investigated the V3 loop evolution of HIV-1 on MVC in relation to coreceptor usage and the nature of HIV-1 quasispecies before MVC therapy using bulk population sequences and ultradeep sequencing. The majority of patients had no detectable minority X4 variant at baseline. The evolution of tropism was followed up until VF and showed three possibilities for viral evolution in these patients: emergence of preexisting X4 variants,
de novo
selection of R5 variants presenting V3 loop mutations, or replication of R5 variants without selection of known mutations.
Influence of intermittent hypoxia interval training on exercise-dependent erythrocyte NOS activation and blood pressure in diabetic patients
Authors: Ladage Dennis , Braunroth Christian , Lenzen Edward , Berghöfer Sandra , Graf Christine , Bloch Wilhelm , Brixius Klara
Published: December 2012

NOS-activation in erythrocytes (eryNOS) is impaired in patients suffering from type 2 diabetes. We investigated the effect of physical exercise on eryNOS activation and whether 6 week hypoxia interval training may alter this process. Male patients with diabetes mellitus type 2 (NIDDM, n = 12; age, 61.3 ± 8.4 years; BMI, 29.8 ± 3.7 kg/m2) underwent physical exercise training before and after 6 week hypoxia interval training. Training was conducted 4 times per week for 90 min at 15.4–12.7 Vol% of inspired oxygen. Vital parameters were recorded. Before hypoxia intervention, eryNOS phosphorylation at serine1177decreased significantly during exercise (basal 17.4 ± 12.0 compared with exercise 8.4 ± 9.2 arbitrary grey values (arGV); P < 0.05). After 6 weeks of hypoxia intervention, eryNOS–pSer1177(2.2 ± 2.5 arGV) was significantly lower at baseline. Ergometry showed an increase (7.6 ± 3.0 arGV; P < 0.05) followed by a decrease to almost baseline levels after 30 min (3.8 ± 1.5 arGV). Maximal exercise capacity and O2-uptake ([Formula: see text]  max) increased significantly. The effects were independent from exercise-induced elevation of blood pressure. Exercise-dependent eryNOS phosphorylation at serine1177was increased similar to that described for the endothelium in diabetic patients. EryNOS dysregulation was partially restored after intermittent hypoxia training.
Carbonic anhydrase II promotes cardiomyocyte hypertrophy
Authors: Brown Brittany F. , Quon Anita , Dyck Jason R.B. , Casey Joseph R.
Published: December 2012

Pathological cardiac hypertrophy, the maladaptive remodelling of the myocardium, often progresses to heart failure. The sodium–proton exchanger (NHE1) and chloride–bicarbonate exchanger (AE3) have been implicated as important in the hypertrophic cascade. Carbonic anhydrase II (CAII) provides substrates for these transporters (protons and bicarbonate, respectively). CAII physically interacts with NHE1 and AE3, enhancing their respective ion transport activities by increasing the concentration of substrate at their transport sites. Earlier studies found that a broad-spectrum carbonic anhydrase inhibitor prevented cardiomyocyte hypertrophy (CH), suggesting that carbonic anhydrase is important in the development of hypertrophy. Here we investigated whether cytosolic CAII was the CA isoform involved in hypertrophy. Neonatal rat ventricular myocytes (NRVMs) were transduced with recombinant adenoviral constructs to over-express wild-type or catalytically inactive CAII (CAII-V143Y). Over-expression of wild-type CAII in NRVMs did not affect CH development. In contrast, CAII-V143Y over-expression suppressed the response to hypertrophic stimuli, suggesting that CAII-V143Y behaves in a dominant negative fashion over endogenous CAII to suppress hypertrophy. We also examined CAII-deficient (Car2) mice, whose hearts exhibit physiological hypertrophy without any decrease in cardiac function. Moreover, cardiomyocytes from Car2 mice do not respond to prohypertrophic stimulation. Together, these findings support a role of CAII in promoting CH.
RELATIVISTIC VECTOR BOSONS UNDER PÖSCHL–TELLER DOUBLE-RING-SHAPED COULOMB POTENTIAL
Authors: HASSANABADI H. , MOLAEE Z. , ZRRINKAMAR S.
Published: December 2012

We study the relativistic Duffin–Kemmer–Petiau equation with the Pöschl–Teller double-ring-shaped Coulomb potential in (1+3) dimensions for spin-1 particles and the exact analytical eigenfunctions and eigenenergies are reported.
GOLDEN- AND PRODUCT-SHAPED HYPERSURFACES IN REAL SPACE FORMS
Authors: CRASMAREANU MIRCEA , HREŢCANU CRISTINA-ELENA , MUNTEANU MARIAN-IOAN
Published: December 2012

We define two classes of hypersurfaces in real space forms, golden- and product-shaped, respectively, by imposing the shape operator to be of golden or product type. We obtain the whole families of above hypersurfaces, based on the classification of isoparametric hypersurfaces, as follows: in the golden case all are hyperspheres, a hyperbolic space and a generalized Clifford torus, while for the product case we obtain the unit hypersphere, the hyperplane, a hypersphere and its associated Clifford torus, respectively, according to the type of the ambient space form namely parabolic, hyperbolic or elliptic, respectively.
F2-Laser-Induced Modification of Aluminum Thin Films into Transparent Aluminum Oxide
Authors: Okoshi Masayuki , Iwai Kazufumi , Nojiri Hidetoshi , Inoue Narumi
Published: December 2012

A vacuum–UV F2 laser of 157 nm wavelength induced strong oxidation of 10-nm-thick Al thin films, forming transparent Al2O3 on silica glass. The laser-induced modification occurred at the surface of Al thin films; consequently, the thickness of the formed Al2O3 thin films increased linearly with increasing number of F2 laser photons. The formation of equivalent-phase Al2O3 thin films was confirmed by X-ray photoelectron spectroscopy. The oxidation reaction in the laser-induced modification of 10-nm-thick Al thin films was slower than that for 20- and 60-nm-thick Al thin films. Morphological changes leading to the crystallization of the Al2O3 thin films were also observed when the thickness of Al thin films increased from 10 to 20 and 60 nm.
Development of Scanning Tunneling Potentiometry for Semiconducting Samples
Authors: Hamada Masayuki , Hasegawa Yukio
Published: December 2012

We have developed a new setup of scanning tunneling potentiometry (STP) applicable to semiconducting samples, which cannot be studied by conventional STP since it measures the local electrostatic potential from a voltage that makes the tunneling current zero. In the new STP setup, the local potential below the tip and its spatial distribution are obtained by measuring the applied voltage that makes the tunneling current fixed at a nonzero value. Using a gold thin film sample we demonstrated the performance of the new STP setup and found that the local potential can be measured in the nonzero tunneling current mode with an energy sensitivity of ∼20 µeV and nanometer-scale spatial resolution.
First-Principles Estimation of Seebeck Coefficient of Bismuth Telluride and Selenide
Authors: Yamamoto Masahiro , Hamada Noriaki
Published: December 2012

The first-principles electronic band structure calculation has been used to examine the relationship between the Bi/Sb composition ratio and the Seebeck coefficient in (Bi1-x
Sb
x
)2Te3. The Te/Se ratio dependence in Bi2(Te1-x
Se
x
)3 has also been investigated and the results have been compared. Because spin–orbit interaction affects the band structure to a large extent, its inclusion is crucial to a quantitative discussion on the Seebeck coefficient. We have found that the Bi/Sb or Te/Se ratio does not have a large effect on the Seebeck coefficient. However, carrier density largely influences the temperature dependence of the Seebeck coefficient. Both the p- and n-type of thermoelectric materials were examined and the results show that their stabilities have the same tendency. The carrier densities in them are largely associated with defects, which suggests that a careful defect control is very important in the production process.
On the Sum of Square Roots of Polynomials and Related Problems
Authors: Kayal Neeraj , Saha Chandan
Published: December 2012

The sum of square roots over integers problem is the task of deciding the sign of a nonzero sum,
S
= ∑
i=1
n
δ
i
· √
a
i
, where
δ
i
∈ {+1, −1} and
a
i
’s are positive integers that are upper bounded by
N
(say). A fundamental open question in numerical analysis and computational geometry is whether ∣
S
∣ ≥ 1/2
(n ·log N)O(1)
when
S
≠ 0. We study a formulation of this problem over polynomials. Given an expression
S
= ∑
i=1
n
c
i
· √
f
i
(
x
), where
c
i
’s belong to a field of characteristic 0 and
f
i
’s are univariate polynomials with degree bounded by
d
and
f
i
(0)≠0 for all
i
, is it true that the minimum exponent of
x
that has a nonzero coefficient in the power series
S
is upper bounded by (
n
·
d
)
O(1)
, unless
S
= 0? We answer this question affirmatively. Further, we show that this result over polynomials can be used to settle (positively) the sum of square roots problem for a special class of integers: Suppose each integer
a
i
is of the form,
a
i
=
X
d
i
+
b
i1
X
di−1
+...+
b
idi
,
d
i
> 0, where
X
is a positive real number and
b
ij
’s are integers. Let
B
= max ({∣
b
ij
∣}
i, j
, 1) and
d
= max
i
{
d
i
}. If
X
> (
B
+ 1)
(n·d)O(1)
then a nonzero
S
= ∑
i=1
n
δ
i
· √
a
i
is lower bounded as ∣
S
∣ ≥ 1/
X
(n·d)O(1)
. The constant in
O
(1), as fixed by our analysis, is roughly 2.

We then consider the following more general problem. Given an arithmetic circuit computing a multivariate polynomial
f
(
X
) and integer
d
, is the degree of
f
(
X
) less than or equal to
d
? We give a coRP
PP
-algorithm for this problem, improving previous results of Allender et al. [2009] and Koiran and Perifel [2007].
Axiomatization of Socio-Economic Principles for Self-Organizing Institutions
Authors: Pitt Jeremy , Schaumeier Julia , Artikis Alexander
Published: December 2012

We address the problem of engineering self-organizing electronic institutions for resource allocation in open, embedded, and resource-constrained systems. In such systems, there is decentralized control, competition for resources and an expectation of both intentional and unintentional errors. The “optimal” distribution of resources is then less important than the endurance of the distribution mechanism. Under these circumstances, we propose to model resource allocation as a common-pool resource management problem, and develop a formal characterization of Elinor Ostrom’s socio-economic principles for self-governing institutions. This article applies a method for sociologically inspired computing to give a complete axiomatization of six of Ostrom’s eight principles in the Event Calculus. A testbed is implemented for experimenting with the axiomatization. The experimental results show that these principles support enduring institutions, in terms of longevity and membership, and also provide insight into calibrating the transaction and running costs associated with implementing the principles against the behavioral profile of the institutional membership. We conclude that it is possible to express Ostrom’s principles in logical form and that they are necessary and sufficient conditions for enduring self-organizing electronic institutions to manage sustainable common-pool resources.