bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of levosulpiride on in vitro motor patterns in the human gastric fundus, antrum, and jejunum
Authors: Gallego D. , Ortega O. , Arenas C. , López I. , Mans E. , Clavé P.
Published: February 2016

Background

Levosulpiride is a 5HT4 agonist/D2 antagonist prokinetic agent used to improve gastric emptying in patients with functional dyspepsia or gastroparesis. The aim of this study was to characterize its effect on the main in vitro motility patterns in the human fundus, antrum, and jejunum.

Methods

Circular muscle strips from human stomach (antrum and fundus) and jejunum, obtained from 46 patients undergoing bariatric surgery, were studied using organ baths. Enteric motor neurons (EMNs) were stimulated by electrical field stimulation (EFS).

Key Results

Levosulpiride, caused an increase in the EFS‐induced cholinergic contractions in the gastric antrum (+37 ± 15.18% at 100 μM, pEC50 = 4.46 ± 0.14; p < 0.05, n = 8) and jejunum (+45.4 ± 22.03% at 100 μM, pEC50 = 3.78 ± 6.81; p < 0.05, n = 5), but not in the gastric fundus. It also caused a slight decrease in tone and frequency of spontaneous contractions in the jejunum, but did not have any major effect on tone or spontaneous contractions in the stomach. It did not have any effect on EFS‐induced relaxations mediated by nitric oxide (NO) in the stomach (antrum and fundus) and by NO and ATP in the jejunum.

Conclusions & Inferences

Our results suggest that the prokinetic effects of levosulpiride in humans are mainly due to the facilitation of the release of acetylcholine by enteric motor neurons in the gastric antrum and the jejunum.
The Effects of Female Sex Hormones on Ventricular Premature Beats and Repolarization Parameters in Physiological Menstrual Cycle
Authors: DOGAN MEHMET , YIGINER OMER , UZ OMER , KUCUK UGUR , DEGIRMENCIOGLU GOKHAN , ISILAK ZAFER , UZUN MEHMET , DAVULCU EZGI
Published: February 2016

Background

The effects of gender difference on cardiac electrophysiology have been well studied. In this study, we aimed to evaluate the effects of estradiol and progesteron changes occuring in physiological menstrual cycle on ventricular premature beats (VPBs) and cardiac repolarization parameters.

Methods

Women of reproductive age with VPBs were included into the study group and healthy women were recruited as the control group. During the menstruation period, a 12‐lead electrocardiography, blood samples, and 24‐hour rhythm Holter were applied to the study group. Similarly, all tests were repeated in the estimated ovulation period (12–14 days before menstruation) by all cases.

Results

The study group consisted of 20 women patients with VPB, and the control group of 18 healthy women. While the number of VPB in the menstruation period was 210 beats/day (interquartile range [IQR]: 1,144), it decreased to 86 beats/day (IQR: 251) in the ovulation period with statistical significance (P < 0.05). Average heart rate in the menstruation period was 81.4 ± 10 beats/min and it significantly increased to 84.6 ± 8 beats/min in the ovulation period (P < 0.05). There were no differences in cardiac repolarization parameters in both menstruation and ovulation periods between the study and control groups. Comparing the menstruation and the ovulation periods, J‐Tpeak interval, which reflects early repolarization, was shorter in the ovulation period (193 ± 27.7 ms and 201.1 ± 28.6 ms, respectively; P < 0.05). Other repolarization parameters did not show any significant difference.

Conclusion

VPB frequency decreases with estradiol peak in the ovulation period. This suggests that estrogen may have protective effects against ventricular arrhythmias.
Prospective investigation on the transfer of Ara h 2, the most potent peanut allergen, in human breast milk
Authors: Schocker Frauke , Baumert Joseph , Kull Skadi , Petersen Arnd , Becker Wolf‐Meinhard , Jappe Uta
Published: February 2016

Background

Peanut allergy is one of the most severe food allergies. Whether breastfeeding induces tolerance to peanuts or on the contrary, pre‐disposes at risk‐babies to occult allergic sensitization to peanuts is still a matter of discussion. We sought to investigate the transfer of the most potent peanut allergen Ara h 2 into human breast milk in a German breast milk study and to shed light on the time kinetics of Ara h 2 appearance.

Methods

We recruited 32 lactating, non‐peanut‐allergic women and collected breast milk samples at different time points after consumption of 100 g dry roasted peanuts. Breast milk samples were investigated for Ara h 2 with different immunological methods: by 2D immunoblotting with a patient's serum, by affinity enrichment using a monoclonal antibody against Ara h 2 followed by LC‐MS/MS‐based detection and by a competitive inhibition ELISA for the detection of Ara h 2 and its digestion‐resistant peptides (DRP‐Ara h 2).

Results

In a qualitative analysis, Ara h 2 could be identified in a breast milk sample by 2D immunoblot by means of a patient's serum and furthermore by immunoaffinity enrichment followed by LC‐MS/MS analysis. In a semi‐quantitative analysis, Ara h 2 and its digestion‐resistant peptides were detected in the breast milk of 9 of 32 subjects. Evidence suggests that Ara h 2 is excreted individually either rapidly (after 1, 2, 3 or 4 h) or delayed (after 8 or 12 h) and in different concentrations.

Conclusions

Time and concentration of secreted Ara h 2 in breast milk appears to be individually regulated. The identification of Ara h 2 in breast milk is the prerequisite for the investigation of its sensitizing or tolerogenic properties.
Vitamin D3 for uncontrolled childhood asthma: A pilot study
Authors: Kerley Conor P. , Hutchinson Katrina , Cormican Liam , Faul John , Greally Peter , Coghlan David , Elnazir Basil
Published: February 2016

Background

Observational and mechanistic data suggest a role for vitamin D in childhood asthma. However, subsequent interventional trials have been inconsistent. We aimed to assess the effect of 15 weeks of vitamin D3 supplementation compared with placebo (PL) in Irish children with asthma.

Methods

We conducted a double‐blind, randomized, PL‐controlled trial of vitamin D supplementation (2000 IU/day) in 44 urban, Caucasian children at high latitude. Assessments were completed at baseline and after 15 weeks of supplementation. Outcome measures were lung function, subjective asthma control and biochemical parameters of total vitamin D, allergy, immunity, airway inflammation, and systemic inflammation. Finally, parents/guardians completed a weekly diary during the trial.

Results

There was no significant difference in baseline 25(OH)D levels, but there was a significant increase in median 25(OH)D in the vitamin D3 group (57.5–105 nmol/l) compared with the PL group (52.5–57.5 nmol/l) (p < 0.0001). There was no significant difference between groups regarding subjective asthma control. Compared with PL, there was a significant decrease in school days missed due to asthma (1 vs. 5 days, p = 0.04) and alkaline phosphatase (−3.4 vs. +16; p = 0.037) in the vitamin D3 group, but there were no beneficial effects regarding several other secondary end‐points. However, there were non‐significant, advantageous changes in the PL group compared with the vitamin D3 group in subjective asthma control and lung function, particularly percentage of predicted forced expiratory volume in 1 s (+2.5 vs. −4; p = 0.06).

Conclusion

Vitamin D3 supplementation led to a significant increase in serum 25(OH)D and decreased school days missed (p = 0.04), but no other advantageous changes in asthma parameters compared with PL. The potential adverse effect of vitamin D deficiency on growth and the potential negative effect of high serum 25(OH)D on pulmonary function warrant further investigation.
Surgery for gastroesophageal reflux disease with Gaucher disease type 2
Authors: Kubo Hiroyuki , Shimono Ryuichi , Tanaka Aya , Fujii Takayuki , Yasuda Saneyuki , Koyano Kosuke , Jinnai Wataru , Kondo Sonoko , Kondo Takeo , Kusaka Takashi
Published: February 2016

Gaucher disease, the most common lysosomal storage disease, is sometimes complicated with gastroesophageal reflux disease (GERD). The present patient was a 136‐day‐old Japanese boy with Gaucher disease type 2. Enzyme replacement therapy and chemical chaperone therapy were successful for the skin disorders, joint contractures, hepatosplenomegaly and thrombocytopenia, but he also had GERD. Accordingly, a Nissen fundoplication with gastrostomy was performed. There was no vulnerability of organs, easy bleeding or difficulty of maintaining the visual field because of hepatosplenomegaly during operation. In the perioperative period, there was no prolonged wound healing or infection. GERD was improved. In the near future, the number of long‐term survivors of Gaucher disease will increase due to improvements in medical therapy. Therefore, it is expected that the number of patients requiring fundoplication will also increase. In patients with successful medical therapy, surgical fundoplication can be safely and effectively performed.
Tympanic ear thermometer assessment of body temperature among patients with cognitive disturbances. An acceptable and ethically desirable alternative?
Authors: Aadal Lena , Fog Lisbet , Pedersen Asger Roer
Published: February 2016

Aim

Investigation of a possible relation between body temperature measurements by the current generation of tympanic ear and rectal thermometers.

Background

In Denmark, a national guideline recommends the rectal measurement. Subsequently, the rectal thermometers and tympanic ear devices are the most frequently used and first choice in Danish hospital wards. Cognitive changes constitute challenges with cooperating in rectal temperature assessments. With regard to diagnosing, ethics, safety and the patients' dignity, the tympanic ear thermometer might comprise a desirable alternative to rectal noninvasive measurement of body temperature during in‐hospital‐based neurorehabilitation.

Design

A prospective, descriptive cohort study. Consecutive inclusion of 27 patients. Linear regression models were used to analyse 284 simultaneous temperature measurements.

Ethics

Ethical approval for this study was granted by the Danish Data Protection Agency, and the study was completed in accordance with the Helsinki Declaration 2008.

Results

About 284 simultaneous rectal and ear temperature measurements on 27 patients were analysed. The patient‐wise variability of measured temperatures was significantly higher for the ear measurements. Patient‐wise linear regressions for the 25 patients with at least three pairs of simultaneous ear and rectal temperature measurements showed large interpatient variability of the association.

Conclusion

A linear relationship between the rectal body temperature assessment and the temperature assessment employing the tympanic thermometer is weak. Both measuring methods reflect variance in temperature, but ear measurements showed larger variation.
The evaluation of neural and vascular hyper‐reactivity for sensitive skin
Authors: Sun L. , Wang X. , Zhang Y. , Wang T. , Li X. , Ma Y.
Published: February 2016

Background

The impaired barrier function has been studied comprehensively but few about the heighted neural and vascular reaction for the pathogenesis of sensitive skin.

Methods

Lactic acid stinging test (LAST) was used to identify sensitive subjects in selection phase. In the subsequent test phase, the baseline value of the blood flow (BF) and the current perception threshold (CPT) was measured by non‐invasive instruments firstly. Then, the 0.001% capsaicin was applied to the nasolabial fold for 5 min. After the capsaicin test (CAT), the BF (immediately after the CAT) and CPT (1 h later after the CAT) were measured again. Blood sample were collected for genetic analysis of four TRPV1 gene single nucleotide polymorphisms between the positive‐group and the negative‐group.

Result

The positive‐group had lower baseline value of CPT at 5 and 250 Hz compared with the negative‐group, but no difference in baseline value of BF. After the CAT, significant variation in CPT at 5 and 250 Hz values and the BF were found in positive‐group but not in negative‐group. The genotype frequencies of AG/GG in RS224534 and AC/CC in RS4790523 in positive‐group were higher than that of negative‐group.

Conclusion

The sensitive subjects were prone to be stimulated by capsaicin to trigger neural and vascular hyper‐reactivity. The genetic variation of TRPV1 and the unpleasant sensation demonstrate that TRPV1 play an important role in the pathogenesis of sensitive skin. Our study supports that sensory irritation inhibitors and anti‐inflammatory compounds should be considered to be added in cosmetics to reduce the heighted neural and vascular reaction of sensitive skin.
Surgical treatment strategy for diabetic forefoot osteomyelitis
Authors: Fujii Miki , Terashi Hiroto , Yokono Koichi
Published: February 2016

The aim of this study was to propose an appropriate surgical treatment for diabetic forefoot osteomyelitis (DFO) involving ischemia or moderate to severe soft tissue infection. The records of 28 patients with osteomyelitis from 2009 to 2015 were retrospectively studied. All patients had undergone surgery based on preoperative magnetic resonance imaging examinations and histopathological or culture analyses confirming the surgical bone margin. The appropriate surgical margin, crucial factors for early healing, and prognosis after complete resection of osteomyelitis were examined. After healing, patients were followed up to assess prognosis (range 32–1,910 days, median 546 days). The healing rate of nonischemic cases of DFO with negative surgical margins was 100% and that of ischemic cases was 84.6%; the ambulatory rates for both types of cases were 100%. No wound (and/or osteomyelitis) recurrence was observed. Nine new cases of DFO developed in six patients (21.4%; eight were due to vascular stenosis, and one was due to biomechanical changes in the foot. After complete resection of osteomyelitis, preoperative and postoperative C‐reactive protein levels and the size of the ulcer were significant predictors of early healing (p < 0.05, 0.01, and 0.05, respectively). The appropriate surgical margin should be set in the area of bone marrow edema, based on magnetic resonance imaging examinations after revascularization. In cases with high preoperative or postoperative C‐reactive protein levels, long‐term antibiotic therapy is recommended, and surgery should be planned after the C‐reactive protein levels decrease, except in emergencies.
Systematic Literature Review and Meta‐Analysis of the Association of Sarcopenia With Mortality
Authors: Chang Shu‐Fang , Lin Pei‐Ling
Published: February 2016

Background

The World Health Organization (2002) indicates that the prevention of frailty is a key indicator of successful aging, and the assessment of the muscular system is the core for determining the frailty syndrome in older adults. Sarcopenia in older adults will affect more than 50 million people and will affect more than 200 million people after 40 years. Systematic literature reviews have yet to focus on the association between sarcopenia and mortality.

Aims

The aims of this study were to determine the correlation between sarcopenia and mortality by using various evaluation methods and to analyze any differences among the resulting correlations of the different assessment tools.

Methods

This study conducted a systematic review of relevant studies in four databases (Cochrane Library, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and Ovid). The inclusion criteria were prospective research, the results included mortality or death, and risk estimates included risk ratio or hazard ratio estimates and 95% confidence intervals. Exclusion criteria included studies that provided no sarcopenia data, the risk of mortality or death, or data indicating deaths from cancers and in hospitals.

Results

This study identified 10 studies that have investigated the association between sarcopenia and mortality with an average follow up of 4.17 years. In total, these studies have sampled 3,797 people and recorded 1,010 deaths. The result suggested that the risk of mortality in the sarcopenia group was higher than that in the nonsarcopenia group.

Linking Evidence to Action

Although the results of evidence‐based studies have suggested that sarcopenia is a geriatric syndrome associated with increased mortality, few studies have focused on decreasing sarcopenia mortality. Therefore, nurse practitioners must be aware of the correlation between sarcopenia and the mortality rate and become actively involved in developing intervention methods for reducing the mortality risk of sarcopenia.
Pinpointing the level of isolation between two cryptic species sharing the same microhabitat: a case study with a scarabaeid species complex
Authors: Roy Lise , Bon Marie‐Claude , Cesarini Cyril , Serin José , Bonato Olivier
Published: February 2016

Understanding the processes of speciation is an important challenge in improving knowledge of the origin of biodiversity. One crucial point is to assess the causes of reproductive isolation, especially in the case of co‐occurring species. Differences in microscale spatial distribution in small organisms may blur the issue. We explored biological processes underlying speciation within dung beetles belonging to thevaccaspecies complex (Scarabaeidae:Onthophagus). The two taxa of this complex,O. vaccaandO. medius,not only are known to have a large overlapping Palearctic distribution range but also share the same cowpat with no physical barriers and no observed specific aggregated patterns in the local distribution. The present study aimed at determining the level of isolation between the two taxa and discusses the most likely scenario of the speciation (sympatry vs. allopatry) based on the Coyne & Orr's (2004) four criteria. We conducted a full study on populations sampled within the Mediterranean region integrating morphological analysis (digital image analysis of the elytral melanism pattern), two‐gene phylogenies, population genetic analyses on populations sampled from an area where both species occur and another one withO. vaccaonly, as well as intra‐ and interspecific mating and crossing bioassays. The variation in the elytral melanism pattern clearly followed a bimodal distribution, withO. mediusbeing more melanic thanO. vacca, with a very limited overlapping area. The two taxa are reproductively isolated, with a strong postzygotic incompatibility despite the absence of sexual isolation. Sequence analysis of both nuclear and mitochondrial markers revealed a deep divergence between the two taxa dating back to 8.7 Mya. All findings concurred with some phenological observations and the conclusion that the most likely scenario for speciation in thevaccacomplex was an allopatric speciation followed by secondary contact.
Cav1.3 (CACNA1D) L‐type Ca2+ channel dysfunction in CNS disorders
Authors: Pinggera Alexandra , Striessnig Jörg
Published: February 2016

Cav1.3 belongs to the family of voltage‐gated L‐type Ca2+ channels and is encoded by the CACNA1D gene. Cav1.3 channels are not only essential for cardiac pacemaking, hearing and hormone secretion but are also expressed postsynaptically in neurons, where they shape neuronal firing and plasticity. Recent findings provide evidence that human mutations in the CACNA1D gene can confer risk for the development of neuropsychiatric disease and perhaps also epilepsy. Loss of Cav1.3 function, as shown in knock‐out mouse models and by human mutations, does not result in neuropsychiatric or neurological disease symptoms, whereas their acute selective pharmacological activation results in a depressive‐like behaviour in mice. Therefore it is likely that CACNA1D mutations enhancing activity may be disease relevant also in humans. Indeed, whole exome sequencing studies, originally prompted to identify mutations in primary aldosteronism, revealed de novo CACNA1D missense mutations permitting enhanced Ca2+ signalling through Cav1.3. Remarkably, apart from primary aldosteronism, heterozygous carriers of these mutations also showed seizures and neurological abnormalities. Different missense mutations with very similar gain‐of‐function properties were recently reported in patients with autism spectrum disorders (ASD). These data strongly suggest that CACNA1D mutations enhancing Cav1.3 activity confer a strong risk for – or even cause – CNS disorders, such as ASD.

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Visual input to the mouse lateral posterior and posterior thalamic nuclei: photoreceptive origins and retinotopic order
Authors: Allen Annette E. , Procyk Christopher A. , Howarth Michael , Walmsley Lauren , Brown Timothy M.
Published: February 2016

Key points

The lateral posterior and posterior thalamic nuclei have been implicated in aspects of visually guided behaviour and reflex responses to light, including those dependent on melanopsin photoreception.

Here we investigated the extent and basic properties of visually evoked activity across the mouse lateral posterior and posterior thalamus.

We show that a subset of retinal projections to these regions derive from melanopsin‐expressing retinal ganglion cells and find many cells that exhibit melanopsin‐dependent changes in firing.

We also show that subsets of cells across these regions integrate signals from both eyes in various ways and that, within the lateral posterior thalamus, visual responses are retinotopically ordered.

In addition to the primary thalamocortical visual relay in the lateral geniculate nuclei, a number of other thalamic regions contribute to aspects of visual processing. Thus, the lateral posterior thalamic nuclei (LP/pulvinar) appear important for various functions including determining visual saliency, visually guided behaviours and, alongside dorsal portions of the posterior thalamic nuclei (Po), multisensory processing of information related to aversive stimuli. However, despite the growing importance of mice as a model for understanding visual system organisation, at present we know very little about the basic visual response properties of cells in the mouse LP or Po. Prompted by earlier suggestions that melanopsin photoreception might be important for certain functions of these nuclei, we first employ specific viral tracing to show that a subset of retinal projections to the LP derive from melanopsin‐expressing retinal ganglion cells. We next use multielectrode electrophysiology to demonstrate that LP and dorsal Po cells exhibit a variety of responses to simple visual stimuli including two distinct classes that express melanopsin‐dependent changes in firing (together comprising ∼25% of neurons we recorded). We also show that subgroups of LP/Po cells integrate signals from both eyes in various ways and that, within the LP, visual responses are retinotopically ordered. Together our data reveal a diverse population of visually responsive neurons across the LP and dorsal Po whose properties align with some of the established functions of these nuclei and suggest new possible routes through which melanopsin photoreception could contribute to reflex light responses and/or higher order visual processing.
Is plasticity within the retrotrapezoid nucleus responsible for the recovery of the set‐point after carotid body denervation in rats?
Authors: Basting Tyler M. , Abe Chikara , Viar Kenneth E. , Stornetta Ruth L. , Guyenet Patrice G.
Published: February 2016

Key points

Arterial is kept constant via breathing adjustments elicited, at least partly, by central chemoreceptors (CCRs) and the carotid bodies (CBs).

The CBs may be active in a normal oxygen environment because their removal reduces breathing. Thereafter, breathing slowly returns to normal. In the present study, we investigated whether an increase in the activity of CCRs accounts for this return.

One week after CB excision, the hypoxic ventilatory reflex was greatly reduced as expected, whereas ventilation and blood gases at rest under normoxia were normal.

Optogenetic inhibition of Phox2b‐expressing neurons including the retrotrapezoid nucleus, a cluster of CCRs, reduced breathing proportionally to arterial pH. The hypopnoea was greater after CB excision but only in a normal or hypoxic environment. The difference could be simply explained by the loss of fast feedback from the CBs.

We conclude that, in rats, CB denervation may not produce CCR plasticity. We also question whether the transient hypoventilation elicited by CB denervation means that these afferents are active under normoxia.

Carotid body denervation (CBD) causes hypoventilation and increases the arterial set‐point; these effects eventually subside. The hypoventilation is attributed to reduced CB afferent activity and the set‐point recovery to CNS plasticity. In the present study, we investigated whether the retrotrapezoid nucleus (RTN), a group of non‐catecholaminergic Phox2b‐expressing central respiratory chemoreceptors (CCRs), is the site of such plasticity. We evaluated the contribution of the RTN to breathing frequency (FR), tidal volume (VT) and minute volume (VE) by inhibiting this nucleus optogenetically for 10 s (archaerhodopsinT3.0) in unanaesthetized rats breathing various levels of O2 and/or CO2. The measurements were made in seven rats before and 6–7 days after CBD and were repeated in seven sham‐operated rats. Seven days post‐CBD, blood gases and ventilation in 21% O2 were normal, whereas the hypoxic ventilatory reflex was still depressed (95.3%) and hypoxia no longer evoked sighs. Sham surgery had no effect. In normoxia or hypoxia, RTN inhibition produced a more sustained hypopnoea post‐CBD than before; in hyperoxia, the responses were identical. Post‐CBD, RTN inhibition reduced FR and VE in proportion to arterial pH or (ΔVE: 3.3 ± 1.5% resting VE/0.01 pHa). In these rats, 20.7 ± 8.9% of RTN neurons expressed archaerhodopsinT3.0. Hypercapnia (3–6% FiCO2) increased FR and VT in CBD rats (n = 4). In conclusion, RTN regulates FR and VE in a pH‐dependent manner after CBD, consistent with its postulated CCR function. RTN inhibition produces a more sustained hypopnoea after CBD than before, although this change may simply result from the loss of the fast feedback action of the CBs.
An Approach for Estimating the Effect of Transient Sweep Through a Resonance
Authors: Hackenberg Hans-Peter , Hartung Andreas
Published: February 2016

The difference of a stationary forced response situation of a turbine or compressor blade relative to a transient resonance sweep is well known and documented in the literature. Different approaches have been used to understand the effect on transient amplitude in comparison with forced response. The dependencies on damping levels and resonance passage speed have been noted. Estimates for a critical or/and maximum sweep velocity have been given. The understanding of transient response during resonance sweep is of practical importance for instance when running a certification stress test for an aircraft engine, where it needs to be decided upfront which acceleration rate (increase in rpm per second) to use to ensure that the maximum airfoil response that could be attained under stationary condition is being measured with sufficient precision. A second reason for understanding of transient response is the verification of correct, if relevant lower, component life usage during transient regimes in operation. This paper gives a proposal for a simple 1D method based on one degree-of-freedom (1DOF) system considerations for estimating the transient response dependency on the sweep velocity, damping levels, and resonance frequency. The method is verified with 3D analyses of more complex blade–disk structures, which have been validated with air jet excitation rig and aero-engine tests. Using the results of the 1DOF analysis, an estimate of the expected stationary resonance response increase can be formulated even in cases where the measured data are based on a significant deviation from the desired sweep velocity, where transient effects would be significant.
Possible mechanisms in atomic force microscope-induced nano-oxidation lithography in epitaxial La0.67Ba0.33MnO3-δ thin films
Authors: Yong Grace J. , Vanderlinde William E. , Tanyi Ekembu Kevin , Schaefer David M. , Stumpf Christopher , Kolagani Rajeswari M.
Published: February 2016

Atomic force microscope (AFM) induced nanolithography has been successfully utilized on perovskite manganite thin films by several groups to create nanoscale patterns for various fundamental mesoscopic-scale transport studies. However, the chemical and physical processes involved have not been understood. This work presents possible microscopic mechanisms for AFM induced nanolithography in La2/3Ba1/3MnO3-δ films induced by an AFM tip, which is negatively biased with respect to the sample in a humid environment. A self-consistent conceptual framework, which accounts for the previously reported observations of changes in the nanomodified regions such as volume increases, selective acid etching, as well as changes in the chemical composition detected by energy dispersive spectroscopy, is reported. Microscopic mechanisms delineated in this work are based on the following: existence of known compounds composed of the available elements (La, Ba, Mn,O, and H) resulting in equal or higher formal oxidation states, postulated electrochemical half reactions resulting in these compounds, reference density and solubility data for these compounds, incorporation of environmental H2O and CO2 by the postulated product solids, electromigration, and electrochemical migration.
Effect of excess hafnium on HfO2 crystallization temperature and leakage current behavior of HfO2/Si metal-oxide-semiconductor devices
Authors: Biswas Debaleen , Singh Manavendra Narayan , Sinha Anil Kumar , Bhattacharyya Satyaranjan , Chakraborty Supratic
Published: February 2016

This article reports the role of excess Hf on the crystallization temperature of thin HfO2 film and leakage current behavior of Hf-rich HfO2/Si metal-oxide-semiconductor (MOS) devices. The HfO2 thin-films deposited by the radio-frequency sputtering system with different Ar:O2 gas mixtures are studied by differential scanning calorimetry. The crystallization temperature of Hf-rich HfO2 film is found to be lower than that of the HfO2 film. The grazing incidence x-ray diffraction studies also confirm the above observation. X-ray photoelectron spectroscopy study further indicates the presence of excess Hf in the oxide film. Enhanced structural relaxation in the presence of excess Hf in HfO2 film releases energy, already stored within the film during deposition, which is responsible for lowering of crystallization temperature. The gate leakage current characteristics are deteriorated in the presence of excess Hf in the HfO2/Si MOS device.
Atomic level analysis of dipeptide biomolecules by a scanning atom probe
Authors: Taniguchi Masahiro , Nishikawa Osamu
Published: February 2016

The biomolecules of dipeptide, α-l-glutamyl-l-glutamic acid and α-l-lysyl-l-lysine, were analyzed by a scanning atom probe (SAP). Single walled carbon nanotubes grown by the high-pressure carbon monoxide process were used to prepare a small ball of tangled carbon nanotubes. Then, the ball was attached to a tungsten tip using silver paste and was dipped into a sample solution of each biomolecule. The air dried specimens were analyzed by SAP at the room temperature applying voltage pulses to trigger field evaporation of the molecules. The number of clusters corresponding to structural functional groups in each of the major mass peaks were counted and compared to the number known to be in the molecule. The results indicate that the SAP analysis is reasonably quantitative.
Accelerated iterative beam angle selection in IMRT
Authors: Bangert Mark , Unkelbach Jan
Published: February 2016

Purpose:

Iterative methods for beam angle selection (BAS) for intensity‐modulated radiation therapy (IMRT) planning sequentially construct a beneficial ensemble of beam directions. In a naïve implementation, the nth beam is selected by adding beam orientations one‐by‐one from a discrete set of candidates to an existing ensemble of (n − 1) beams. The best beam orientation is identified in a time consuming process by solving the fluence map optimization (FMO) problem for every candidate beam and selecting the beam that yields the largest improvement to the objective function value. This paper evaluates two alternative methods to accelerate iterative BAS based on surrogates for the FMO objective function value.

Methods:

We suggest to select candidate beams not based on the FMO objective function value after convergence but (1) based on the objective function value after five FMO iterations of a gradient based algorithm and (2) based on a projected gradient of the FMO problem in the first iteration. The performance of the objective function surrogates is evaluated based on the resulting objective function values and dose statistics in a treatment planning study comprising three intracranial, three pancreas, and three prostate cases. Furthermore, iterative BAS is evaluated for an application in which a small number of noncoplanar beams complement a set of coplanar beam orientations. This scenario is of practical interest as noncoplanar setups may require additional attention of the treatment personnel for every couch rotation.

Results:

Iterative BAS relying on objective function surrogates yields similar results compared to naïve BAS with regard to the objective function values and dose statistics. At the same time, early stopping of the FMO and using the projected gradient during the first iteration enable reductions in computation time by approximately one to two orders of magnitude. With regard to the clinical delivery of noncoplanar IMRT treatments, we could show that optimized beam ensembles using only a few noncoplanar beam orientations often approach the plan quality of fully noncoplanar ensembles.

Conclusions:

We conclude that iterative BAS in combination with objective function surrogates can be a viable option to implement automated BAS at clinically acceptable computation times.
Multimodal acquisition of articulatory data: Geometrical and temporal registration
Authors: Aron Michaël , Berger Marie-Odile , Kerrien Erwan , Wrobel-Dautcourt Brigitte , Potard Blaise , Laprie Yves
Published: February 2016

Acquisition of dynamic articulatory data is of major importance for studying speech production. It turns out that one technique alone often is not enough to get a correct coverage of the whole vocal tract at a sufficient sampling rate. Ultrasound (US) imaging has been proposed as a good acquisition technique for the tongue surface because it offers a good temporal sampling, does not alter speech production, is cheap, and is widely available. However, it cannot be used alone and this paper describes a multimodal acquisition system which uses electromagnetography sensors to locate the US probe. The paper particularly focuses on the calibration of the US modality which is the key point of the system. This approach enables US data to be merged with other data. The use of the system is illustrated via an experiment consisting of measuring the minimal tongue to palate distance in order to evaluate and design Magnetic Resonance Imaging protocols well suited for the acquisition of three-dimensional images of the vocal tract. Compared to manual registration of acquisition modalities which is often used in acquisition of articulatory data, the approach presented relies on automatic techniques well founded from geometrical and mathematical points of view.
Fast evaluation of transient acoustic fields
Authors: Carley Michael
Published: February 2016

The efficient computation of transient fields radiated by non-harmonic source distributions is a problem relevant in numerous areas of acoustics. This paper presents an efficient easily implemented method for the generation of time-dependent spherical harmonic expansions for arbitrary sources, which can be used to compute the transient radiated field at arbitrary points outside the source domain. The method depends on the theory of time-domain spherical harmonic expansions and the solution of Vandermonde systems. Results are presented demonstrating the efficiency and accuracy of the method with respect to full evaluation of the field radiated by a randomized source distribution.
Five-Antigen Fluorescent Bead-Based Assay for Diagnosis of Lyme Disease
Authors: Embers Monica E. , Hasenkampf Nicole R. , Barnes Mary B. , Didier Elizabeth S. , Philipp Mario T. , Tardo Amanda C.
Published: February 2016

The systematically difficult task of diagnosing Lyme disease can be simplified by sensitive and specific laboratory tests. The currently recommended two-tier test for serology is highly specific but falls short in sensitivity, especially in the early acute phase. We previously examined serially collected serum samples from
Borrelia burgdorferi
-infected rhesus macaques and defined a combination of antigens that could be utilized for detection of infection at all phases of disease in humans. The five
B. burgdorferi
antigens, consisting of OspC, OspA, DbpA, OppA2, and the C6 peptide, were combined into a fluorescent cytometric bead-based assay for the detection of
B. burgdorferi
antigen-specific IgG antibodies. Samples from Lyme disease patients and controls were used to determine the diagnostic value of this assay. Using this sample set, we found that our five-antigen multiplex IgG assay exhibited higher sensitivity (79.5%) than the enzyme immunoassay (EIA) (76.1%), the two-tier test (61.4%), and the C6 peptide enzyme-linked immunosorbent assay (ELISA) (77.2%) while maintaining specificity over 90%. When detection of IgM was added to the bead-based assay, the sensitivity improved to 91%, but at a cost of reduced specificity (78%). These results indicate that the rational combination of antigens in our multiplex assay may offer an improved serodiagnostic test for Lyme disease.
Comparison of Fecal Microbiota between German Holstein Dairy Cows with and without Left-Sided Displacement of the Abomasum
Authors: Song Eun-Sik , Jung Sang Il , Park Hyung-Jin , Seo Kyoung-Won , Son Jeong-Hoon , Hong Sanghyun , Shim Minkyung , Kim Hyeun Bum , Song Kun-Ho
Published: February 2016

One of the most common diseases in high-performance German Holstein dairy cows is left-sided displacement of the abomasum (LDA). Hypomotility of the abomasum is detrimental during the pathogenesis of LDA. It is known that improper interactions between the gut microbiota and the enteric nervous system contribute to dysfunctions of gastrointestinal motility. Therefore, we hypothesized that the gut microbial composition will be different between German Holstein dairy cows with and without LDA. We used 16S rRNA gene analysis to evaluate whether there are any differences in bacterial composition between German Holstein dairy cows with and without LDA. Even though our data are limited to being used to correlate compositional changes with corresponding functional aspects in the pathogenesis of LDA, results from this study show that the fecal microbial compositions of German Holstein dairy cows with LDA shifted and were less diverse than those in normal cows. In particular,Spirochaeteswere absent in cows with LDA.
Accurate Serodetection of Asymptomatic Leishmania donovani Infection by Use of Defined Antigens
Authors: Vallur Aarthy C. , Reinhart Caroline , Mohamath Raodoh , Goto Yasuyuki , Ghosh Prakash , Mondal Dinesh , Duthie Malcolm S. , Reed Steven G.
Published: February 2016

Infection with
Leishmania donovani
is typically asymptomatic, but a significant number of individuals may progress to visceral leishmaniasis (VL), a deadly disease that threatens 200 million people in areas where it is endemic. While diagnosis of acute VL has been simplified by the use of cost-effective confirmatory serological tests, similar standardized tools are not widely available for detecting asymptomatic infection, which can be 4 to 20 times more prevalent than active disease. A simple and accurate serological test that is capable of detecting asymptomatic
L. donovani
infection will be useful for surveillance programs targeting VL control and elimination. To address this unmet need, we evaluated recombinant antigens for their ability to detect serum antibodies in 104 asymptomatic
L. donovani
-infected individuals (qualified as positive for
L. donovani
-specific antibodies by direct agglutination test [DAT]) from the Mymensingh district of Bangladesh where VL is hyperendemic. The novel proteins rKR95 and rTR18 possessed the greatest potential and detected 69% of DAT-positive individuals, with rKR95 being more robust in reactivity. Agreement in results for individuals with high DAT responses, who are more likely to progress to VL disease, was 74%. When considered along with rK39, a gold standard antigen that is used to confirm clinical diagnosis of VL but that is now becoming widely used for surveillance, rKR95 and rTR18 conferred a sensitivity of 84% based on a theoretical combined estimate. Our data indicate that incorporating rKR95 and rTR18 with rK39 in serological tests amenable to rapid or high-throughput screening may enable simple and accurate detection of asymptomatic infection. Such tests will be important tools to measure
L. donovani
infection rates, a primary goal in surveillance and a critical measurement with which to assess elimination programs.
Evaluation of MALDI Biotyper Mycobacteria Library v3.0 for Identification of Nontuberculous Mycobacteria
Authors: Rodríguez-Sánchez Belén , Ruiz-Serrano M. Jesús , Ruiz Adrián , Timke Markus , Kostrzewa Markus , Bouza Emilio
Published: February 2016

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has demonstrated its ability to promptly identify nontuberculous mycobacteria using the Mycobacteria Library v2.0. However, some species are particularly difficult to identify reliably using this database, providing a low log(score). In this study, the identification power of an updated Mycobacteria Library (v3.0) has been evaluated. Overall, 109 NTM isolates were analyzed with both databases. The v3.0 database allowed a high-level confidence in the identification [log(score) value, ≥1.8] of 91.7% of the isolates versus 83.5% with the v2.0 version (
P
< 0.01).
gD-Independent Superinfection Exclusion of Alphaherpesviruses
Authors: Criddle A. , Thornburg T. , Kochetkova I. , DePartee M. , Taylor M. P.
Published: February 2016

Many viruses have the capacity to prevent a cell from being infected by a second virus, often termed superinfection exclusion. Alphaherpesviruses, including the human pathogen herpes simplex virus 1 (HSV-1) and the animal herpesvirus pseudorabies virus (PRV), encode a membrane-bound glycoprotein, gD, that can interfere with subsequent virion entry. We sought to characterize the timing and mechanism of superinfection exclusion during HSV-1 and PRV infection. To this end, we utilized recombinant viruses expressing fluorescent protein (FP) markers of infection that allowed the visualization of viral infections by microscopy and flow cytometry as well as the differentiation of viral progeny. Our results demonstrated the majority of HSV-1- and PRV-infected cells establish superinfection exclusion by 2 h postinfection. The modification of viral infections by virion inactivation and phosphonoacetic acid, cycloheximide, and actinomycin D treatments indicated new protein synthesis is needed to establish superinfection exclusion. Primary infection with gene deletion PRV recombinants identified that new gD expression is not required to establish superinfection exclusion of a secondary viral inoculum. We also identified the timing of coinfection events during axon-to-cell spread, with most occurring within a 2-h window, suggesting a role for cellular superinfection exclusion during neuroinvasive spread of infection. In summary, we have characterized a gD-independent mechanism of superinfection exclusion established by two members of the alphaherpesvirus family and identified a potential role of exclusion during the pathogenic spread of infection.

IMPORTANCE
Superinfection exclusion is a widely observed phenomenon initiated by a primary viral infection to prevent further viruses from infecting the same cell. The capacity for alphaherpesviruses to infect the same cell impacts rates of interviral recombination and disease. Interviral recombination allows genome diversification, facilitating the development of resistance to antiviral therapeutics and evasion of vaccine-mediated immune responses. Our results demonstrate superinfection exclusion occurs early, through a gD-independent process, and is important in the directed spread of infection. Identifying when and where in an infected host viral genomes are more likely to coinfect the same cell and generate viral recombinants will enhance the development of effective antiviral therapies and interventions.
The Herpes Simplex Virus Latency-Associated Transcript Gene Is Associated with a Broader Repertoire of Virus-Specific Exhausted CD8
+
T Cells Retained within the Trigeminal Ganglia of Latently Infected HLA Transgenic Rabbits
Authors: Srivastava Ruchi , Dervillez Xavier , Khan Arif A. , Chentoufi Aziz A. , Chilukuri Sravya , Shukr Nora , Fazli Yasmin , Ong Nicolas N. , Afifi Rasha E. , Osorio Nelson , Geertsema Roger , Nesburn Anthony B. , Wechsler Steven L. , BenMohamed Lbachir
Published: February 2016

Persistent pathogens, such as herpes simplex virus 1 (HSV-1), have evolved a variety of immune evasion strategies to avoid being detected and destroyed by the host's immune system. A dynamic cross talk appears to occur between the HSV-1 latency-associated transcript (LAT), the only viral gene that is abundantly transcribed during latency, and the CD8
+
T cells that reside in HSV-1 latently infected human and rabbit trigeminal ganglia (TG). The reactivation phenotype of TG that are latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT
+
TG) is significantly higher than TG latently infected with LAT-null mutant (i.e., LAT
−
TG). Whether LAT promotes virus reactivation by selectively shaping a unique repertoire of HSV-specific CD8
+
T cells in LAT
+
TG is unknown. In the present study, we assessed the frequency, function, and exhaustion status of TG-resident CD8
+
T cells specific to 40 epitopes derived from HSV-1 gB, gD, VP11/12, and VP13/14 proteins, in human leukocyte antigen (HLA-A*0201) transgenic rabbits infected ocularly with LAT
+
versus LAT
–
virus. Compared to CD8
+
T cells from LAT
–
TG, CD8
+
T cells from LAT
+
TG (i) recognized a broader selection of nonoverlapping HSV-1 epitopes, (ii) expressed higher levels of PD-1, TIM-3, and CTLA-4 markers of exhaustion, and (iii) produced less tumor necrosis factor alpha, gamma interferon, and granzyme B. These results suggest a novel immune evasion mechanism by which the HSV-1 LAT may contribute to the shaping of a broader repertoire of exhausted HSV-specific CD8
+
T cells in latently infected TG, thus allowing for increased viral reactivation.

IMPORTANCE
A significantly larger repertoire of dysfunctional (exhausted) HSV-specific CD8
+
T cells were found in the TG of HLA transgenic rabbits latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT
+
TG) than in a more restricted repertoire of functional HSV-specific CD8
+
T cells in the TG of HLA transgenic rabbits latently infected with LAT-null mutant (i.e., LAT
–
TG). These findings suggest that the HSV-1 LAT locus interferes with the host cellular immune response by shaping a broader repertoire of exhausted HSV-specific CD8
+
T cells within the latency/reactivation TG site.