bluuebunny/crossref_metadata_2025 huggingface dataset:
A parabolic equation method for predicting sound propagation above and below a layered ground
Authors: Tao Hongdan , Li Kai MIng
Published: October 2011

A numerical model based on a wide-angle parabolic equation (PE) technique has been developed for calculating the sound fields above and below a layered ground. A finite element discretization was applied along the vertical direction instead of the classical finite difference scheme. By using the finite element approach, the boundary conditions, i.e., the continuity of pressure and velocity, can be incorporated directly at the air/ground and ground/ground interfaces. The range-dependent sound fields were obtained by marching the finite-element solutions (above and below the layered ground) in the radial direction. This paper reports a preliminary formulation and presents some initial computational results for the sound fields above and below a porous ground. The numerical results from the PE calculations were compared with the results obtained from analytical solutions for and other benchmark results. A linear and cubic Hermite interpolate function was used in the numerical formulations for the finite element model. It has been shown that use of the cubic Hermite interpolation function generally leads to more accurate numerical solutions with fewer elements. [Work partially funded by Federal Aviation Administration and the China Research Scholarship Council.]
Active control of a centrifugal fan in a mock laptop enclosure
Authors: Esplin J. James , Boyle John K. , Sommerfeldt Scott D. , Gee Kent L.
Published: October 2011

Active noise control (ANC) has shown promise in minimizing the effect of fan noise on users. Recent research by the authors has developed a model which is used to implement ANC on the inlets of centrifugal cooling fans. This model is based on minimizing radiated acoustic power in a model of the fan radiation and using those results to determine appropriate nearfield locations for the error sensor(s). Though this approach has been experimentally verified in an idealized setting, it was not verified in a more realistic situation. This paper describes how this model was expanded from its idealized setting to a mock laptop enclosure. When necessary modifications to the model were made, tonal noise can be predicted in the nearfield of the fan inlets, which allows one to develop an effective compact, realistic ANC setup for use in the mock laptop enclosure. With this ANC setup, significant global reduction of the inlet tonal noise can be achieved.
Rhythm, tempo, and F0 in language discrimination
Authors: Rodriquez Tara , Arvaniti Amalia
Published: October 2011

Existing literature on language rhythm suggests that languages can be discriminated in AAX “oddball” experiments only if they belong to different rhythm classes. Since exceptions to this pattern have been noted (e.g., the discrimination of Polish from English though both are said to be stress-timed), a series of five AAX experiments was run to test whether successful discrimination depends on factors other than rhythm class. English utterances were used as the base (AA) with Polish, Greek, Korean, Spanish, and Danish as the target languages. The stimuli were converted to sasasa while either retaining their original F0 or with flat F0; further, either the original tempo of each stimulus was retained or the stimuli (within each experiment) were manipulated to all have the same tempo (2 * 2 overall design, tempo * F0). The results show that tempo played the major role in discrimination with F0 cues being used when tempo differences between the two languages were eliminated. Rhythm class, on the other hand, played no significant part in discrimination suggesting that previous experiments may have interpreted as an effect of rhythm class the fact that tempo is often (though not always) slower in languages classified as stress-timed.
Duration of American English vowels and its effects on intelligibility for native and non-native speakers
Authors: Chen Chia-Tsen , Liu Chang , Jin Su-Hyun
Published: October 2011

Durations of 12 American English vowels were measured for English-, Chinese-, and Korean-native speakers. Results showed that vowel duration was significantly affected by speaker groups. That is, vowels produced by English- and Korean-native speakers were significantly longer than vowels produced by Chinese-native speakers. The patterns of vowel duration as a function of vowel category were quite similar between native and non-native speakers. However, Mandarin Chinese vowels did not differ in duration across Chinese-native speakers, while durations of Korean vowels were significantly different across Korean-native speakers. These results suggest that non-native speakers were able to follow the duration pattern of native speakers in their vowel production. When vowel duration was equalized across vowel category with the central vowel nucleus remained, vowel intelligibility significantly dropped about 5% compared to vowels presented in the syllabic context for native and non-native speakers. The perceptual effects of vowel duration on vowel intelligibility appeared to be the same for native and non-native speakers, independent of speaker language background and the second language proficiency level.
Sharing the beginning versus sharing the end: Spoken word recognition in the visual world paradigm in Japanese
Authors: Teruya Hideko , Kapatsinski Vsevolod
Published: October 2011

Several studies have suggested that in English spoken word recognition, words sharing beginnings compete more than words sharing ends (i.e., the cohort competitor has an advantage relative to the rime competitor). We investigated the relative activation differences between the cohort competitor and the rime competitor in Japanese CVCV words using the visual-world paradigm (Allopenna et al., 1998). Results were analyzed using linear mixed effects models (Magnuson et al., 2008). Participants fixated referents of rime competitors more than those of cohort competitors when the cohort competitor shared only the first consonant with the target while the rime shared the rest of the word (VCV). When both competitors shared a syllable with the target, the rime competitor was fixated as much as the cohort competitor and the recognition of the target was delayed. The results suggest a syllabic or moraic basis to Japanese spoken word recognition, where lexical activation requires at least one mora of the word to match the signal. The weakness of cohort effects in Japanese challenge fully incremental models of word recognition. Whether the results would also hold for English is unclear as previous visual world spoken word recognition studies in English did not systematically manipulate degree of overlap.
Korean perception of the Japanese voiceless alveolar fricative /s/
Authors: Simpson Heather E.
Published: October 2011

Korean voiceless obstruents exhibit a relatively unique phonemic contrast based on laryngeal activity, a three-way tense, lax, and aspirated contrast for stops and affricates and a two-way tense and lax contrast for the alveolar fricative /s/. The relative primacy of various cues to the distinction, particularly for the affricate and fricative contrasts, remains controversial. Patterns in the adaptation of English loanwords have been used to infer the phonological basis for the mapping of English /s/ to Korean, however perception studies have shown that loanword adaptations do not fully account for the synchronic phonological mapping from English loans by Korean native speakers (Schmidt 1996). Mapping from Japanese /s/ to Korean has been much less studied, but according to a loanword study by Ito et al. (2006), Japanese /s/ in word-initial and medial position is consistently mapped to Korean lax /s/, and geminate /s/ is consistently mapped to Korean tense /s*/. However, there appears to have been no comparable perception study to show synchronic mapping by Korean native speakers. The current study undertakes a preliminary evaluation of perceptual mapping of Japanese /s/ to Korean and finds that though the word initial Japanese /s/ conforms to loan-word predictions, word-medial /s/ does not.
Perception of initial stops in tonal and non-tonal Korean
Authors: Lee Hyunjung , Jongman Allard
Published: October 2011

The current study investigated the perception of the three-way distinction among voiceless stops in non-tonal Seoul Korean and tonal Kyungsang Korean. We addressed whether listeners from these two dialects differ in the way they perceive the three stops. Twenty Korean listeners (nine from Seoul and eleven from Kyungsang) were tested with stimuli in which VOT and F0 were systematically manipulated. Analyses of the perceptual identification functions show that the results replicate the reported phonetic trading relationship between VOT and F0 in Seoul Korean and that this trading relationship is observed in Kyungsang as well. However, the trading relationship differs between the two dialects. Logistic regression analysis further shows that the two dialects use the perceptual cues differently. While both VOT and F0 are effective for Seoul Korean, only VOT is effective for the identification of all three stops for Kyungsang Korean. A similar pattern has been observed acoustically [Lee and Jongman, J. Acoust. Soc. Am. 127 (3), 2023–2023 (2010)]. The results will be discussed in terms of the close link between perception and production across the two different dialects.
Effects of speaker variability and noise on identifying Mandarin fricatives by native and non-native listeners
Authors: Lee Chao-Yang , Zhang Yu , Li Ximing , Tao Liang , Bond Z. S.
Published: October 2011

A fundamental issue in speech perception is how listeners with different characteristics deal with various sources of acoustic variability. This study examined how speaker variability and noise affected native and nonnative identification of the place contrast in voiceless Mandarin fricatives. Monosyllabic Mandarin words fa, sa, xia, and sha produced by three female and three male speakers were mixed with five levels of speech-shaped noise. The stimuli were presented either blocked by speaker or mixed across speakers to 40 native Mandarin listeners and 52 English-speaking listeners with various amounts of Mandarin experience. It was predicted that the mixed presentation and noise would affect nonnative identification to a greater extent because of the imperfect knowledge of the target language. The results showed that nonnative performance was compromised to a greater extent by noise but not by speaker variability. These results were compared to previous studies which compared native and nonnative perception of segmental and suprasegmental contrasts in other adverse conditions. It was concluded that not all sources of acoustic variability affect native and nonnative speech perception similarly.
Phonemic perception under noise condition by early and late learners of English
Authors: Harada Tetsuo
Published: October 2011

This study investigated long-term age effects of minimal input in an English as a foreign language (EFL) environment on the perception of English phonemes. Ten native speakers of American English, 10 university students who started studying English in Japan for a few hours a week between ages of three and eight (early learners), and 10 university students who began study in junior high school at the age of 12 or 13 (late learners) participated in a phonemic discrimination test. The selected target phonemes were tense vs. lax vowels ([i, ɪ], [u, U]) and word-initial approximants ([l,r]). Three monosyllabic words were selected for each phoneme (e.g., beat, bit). Each pair of words was tested as six different tri-word trials (e.g., AAB, ABA) with and without the presence of a white noise. The participants were asked to choose the odd out in each trial. Results showed that although the early and late learners did not significantly differ across the phonemes in the discrimination test given without any noise, the former outperformed the latter under noise condition (p < 0.05). The findings support Lin et al.'s (2004) hypothesis that early learners are likely to establish more robust phonemic categories than late learners.
Wallace Clement Sabine Award of the Acoustical Society of America
Authors: Jaffe J. Christopher
Published: October 2011

The Wallace Clement Sabine Award is presented to an individual of any nationality who has furthered the knowledge of architectural acoustics, as evidenced by contributions to professional journals and periodicals or by other accomplishments in the field of architectural acoustics.
The Diets of Early Hominins
Authors: Ungar Peter S. , Sponheimer Matt
Published: October 2011

Diet changes are considered key events in human evolution. Most studies of early hominin diets focused on tooth size, shape, and craniomandibular morphology, as well as stone tools and butchered animal bones. However, in recent years, dental microwear and stable isotope analyses have hinted at unexpected diversity and complexity in early hominin diets. Some traditional ideas have held; others, such as an increasing reliance on hard-object feeding and a dichotomy between
Australopithecus
and
Paranthropus
, have been challenged. The first known evidence of C
4
plant (tropical grasses and sedges) and hard-object (e.g., seeds and nuts) consumption dates to millions of years after the appearance of the earliest probable hominins, and there are no consistent trends in diet change among these species through time.
Nanoparticle Superlattice Engineering with DNA
Authors: Macfarlane Robert J. , Lee Byeongdu , Jones Matthew R. , Harris Nadine , Schatz George C. , Mirkin Chad A.
Published: October 2011

Design rules allow the synthesis of nanoparticle-DNA superlattices in nine different lattices.
Successful Transmission of a Retrovirus Depends on the Commensal Microbiota
Authors: Kane Melissa , Case Laure K. , Kopaskie Karyl , Kozlova Alena , MacDearmid Cameron , Chervonsky Alexander V. , Golovkina Tatyana V.
Published: October 2011

Commensal microflora promote the pathogenesis of mucosally acquired viruses.
Self-Assembly Enters the Design Era
Authors: Travesset Alex
Published: October 2011

A set of simple rules is used to design and control the self-assembly of nanoparticles into complex structures.
Keeping Bacteria at a Distance
Authors: Johansson Malin E.V. , Hansson Gunnar C.
Published: October 2011

An antibacterial peptide is essential for restricting contact between the intestinal microbiota and host.
The Costs of Breathing
Authors: Lane Nick
Published: October 2011

Selection for respiratory function has implications for organism fitness, fertility, and life span.
First Report of a Brain Abscess Caused by Nocardia veterana
Authors: Arends J. E. , Stemerding A. M. , Vorst S. P. , de Neeling A. J. , Weersink A. J. L.
Published: October 2011

Among
Nocardia
species causing infections,
Nocardia veterana
is rarely isolated and is mostly described as causing pulmonary infections. This is the first presentation of a case of brain abscess attributable to an
N. veterana
infection in a patient with type 2 diabetes. Prolonged antibiotic therapy with trimethoprim-sulfamethoxazole led to successful clinical recovery.
IMP-Producing Carbapenem-Resistant Klebsiella pneumoniae in the United States
Authors: Limbago Brandi M. , Rasheed J. Kamile , Anderson Karen F. , Zhu Wenming , Kitchel Brandon , Watz Nancy , Munro Susan , Gans Hayley , Banaei Niaz , Kallen Alex J.
Published: October 2011

The emergence and spread of carbapenem-resistant
Enterobacteriaceae
(CRE) producing acquired carbapenemases have created a global public health crisis. In the United States, CRE producing the
Klebsiella pneumoniae
carbapenemase (KPC) are increasingly common and are endemic in some regions. Metallo-β-lactamase (MBL)-producing CRE have recently been reported in the United States among patients who received medical care in countries where such organisms are common. Here, we describe three carbapenem-resistant
K. pneumoniae
isolates recovered from pediatric patients at a single U.S. health care facility, none of whom had a history of international travel. The isolates were resistant to carbapenems but susceptible to aztreonam, trimethoprim-sulfamethoxazole, and fluoroquinolones. The three isolates were closely related to each other by pulsed-field gel electrophoresis and contained a common plasmid. PCR and sequence analysis confirmed that these isolates produce IMP-4, an MBL carbapenemase not previously published as present among
Enterobacteriaceae
in the United States.
Cholesterol Depletion of Hepatoma Cells Impairs Hepatitis B Virus Envelopment by Altering the Topology of the Large Envelope Protein
Authors: Dorobantu Cristina , Macovei Alina , Lazar Catalin , Dwek Raymond A. , Zitzmann Nicole , Branza-Nichita Norica
Published: October 2011

Previous reports have shown that cholesterol depletion of the membrane envelope of the hepatitis B virus (HBV) impairs viral infection of target cells. A potential function of this lipid in later steps of the viral life cycle remained controversial, with secretion of virions and subviral particles (SVP) being either inhibited or not affected, depending on the experimental approach employed to decrease the intracellular cholesterol level. This work addressed the role of host cell cholesterol on HBV replication, assembly, and secretion, using an alternative method to inhibition of the enzymes involved in the biosynthesis pathway. Growing HBV-producing cells with lipoprotein-depleted serum (LPDS) resulted in an important reduction of the amount of cholesterol within 24 h of treatment (about 40%). Cell exposure to chlorpromazine, an inhibitor of the clathrin-mediated pathway used by the low-density lipoprotein receptor for endocytosis, also impacted the cholesterol level; however, this level of inhibition was not achievable when the synthesis inhibitor lovastatin was used. HBV secretion was significantly inhibited in cholesterol-depleted cells (by ∼80%), while SVP release remained unaffected. The viral DNA genome accumulated in LPDS-treated cells in a time-dependent manner. Specific immunoprecipitation of nucleocapsids and mature virions revealed an increased amount of naked nucleocapsids, while synthesis of the envelope proteins occurred as normally. Following analysis of the large envelope protein conformation in purified microsomes, we concluded that cholesterol is important in maintaining the dual topology of this polypeptide, which is critical for viral envelopment.
Determination of the psychometric properties of a behavioural marking system for obstetrical team training using high-fidelity simulation: Table 1
Authors: Morgan Pamela J , Tregunno Deborah , Pittini Richard , Tarshis Jordan , Regehr Glenn , Desousa Susan , Kurrek Matt , Milne Ken
Published: October 2011

Background

To determine the effectiveness of high-fidelity simulation for team training, a valid and reliable tool is required. This study investigated the internal consistency, inter-rater reliability and test–retest reliability of two newly developed tools to assess obstetrical team performance.

Methods

After research ethics board approval, multidisciplinary obstetrical teams participated in three sessions separated by 5–9 months and managed four high-fidelity simulation scenarios. Two tools, an 18-item Assessment of Obstetric Team Performance (AOTP) and a six-item Global Assessment of Obstetric Team Performance (GAOTP) were used.5Eight reviewers rated the DVDs of all teams' performances.

Results

Two AOTP items were consistently incomplete and omitted from the analyses. Cronbach's α for the 16-item AOTP was 0.96, and 0.91 for the six-item GAOTP. The eight-rater α for the GAOTP was 0.81 (single-rater intra-class correlation coefficient, 0.34) indicating acceptable inter-rater reliability. The ‘four-scenario’ α for the 12 teams was 0.79 for session 1, 0.88 for session 2, and 0.86 for session 3, suggesting that performance is not being strongly affected by the context specificity of the cases. Pearson's correlation of team performance scores for the four scenarios were 0.59, 0.35, 0.40 and 0.33, and for the total score across scenarios it was 0.47, indicating moderate test–retest reliability.

Conclusions

The results from this study indicate that the GAOTP would be a sufficient assessment tool for obstetrical team performance using simulation provided that it is used to assess teams with at least eight raters to ensure a sufficiently stable score. This could allow the quantitative evaluation of an educational intervention.
Three episodes of crustal development in the Rehoboth Province, Namibia
Authors: Van Schijndel Valby , Cornell David H. , Hoffmann K.-H. , Frei Dirk
Published: October 2011

The African continental crust was assembled by a series of orogenies over a period of billions of years mainly in Precambrian times. Tracing the build-up history of this stable crust is not always straightforward due to multiphase deformation and regions with poor outcrop. Episodes of metamorphism and magmatism associated with multiple Wilson cycles are recorded in zircons, which found their way into sediments derived from the hinterland. Dating of zircon populations in detrital rocks can hence provide age spectra which reflect the metamorphic and magmatic events of the region. Microbeam dating of detrital zircon is used to characterize the crustal development history of the Rehoboth Province of southern Africa. We investigated a quartzite of the Late Palaeo-Early Mesoproterozoic Billstein Formation, formed in a continental basin, and a quartz-feldspar arenite layer of the late Mesoproterozoic Langberg Formation conglomerates, immature sediments formed within a felsic volcanic system (both close to Rehoboth Town). The combined data indicate three episodes of crustal evolution in the Rehoboth Province. The oldest phase is only documented in the Billstein quartzite by three 2.98–2.7 Ga Archaean zircons. A Palaeoproterozoic phase between 2.2 and 1.9 Ga is older than any known exposures of the Rehoboth Province. The Billstein quartzite shows a main peak at 1.87 Ga, corresponding to the 1863±10 Ma Elim Formation. The Langberg sample reflects magmatism related to the entire Namaqua–Natal Wilson cycle between
c.
1.32 and 1.05 Ga. The absence of zircons of that age range in the Billstein quartzite indicates a pre-Namaqua age for the Billstein Formation. Our data shows that there were at least three episodes of crustal development at 2.98–2.7 Ga, 2.05–1.75 and 1.32–1.1 Ga. We have documented the existence of a previously unrecognized 2.98–2.7 Ga Archaean crustal component, which was probably exposed in the Rehoboth Province during the Palaeoproterozoic and thus indicates a much longer geological history for the Rehoboth Province than previously known.
Morphology, internal architecture and emplacement mechanisms of lava flows from the Central Atlantic Magmatic Province (CAMP) of Argana Basin (Morocco)
Authors: Hachimi Hind El , Youbi Nasrrddine , Madeira José , Bensalah Mohamed Khalil , Martins Línia , Mata João , Medina Fida , Bertrand Hervé , Marzoli Andrea , Munhá José , Bellieni Giuliano , Mahmoudi Abdelkader , Abbou Mohamed Ben , Assafar Hicham
Published: October 2011

The morphology, internal architecture and emplacement mechanisms of the Central Atlantic Magmatic Province (CAMP) lava flows of Argana Basin in Morocco are presented. The volcanic pile was produced by two volcanic pulses. The first, represented by the Tasguint Formation, corresponds to a succession of 3–13 individual flows created by 1–8 eruptions; the second, Alemzi Formation, is composed of 2–7 individual flows formed by 1–4 eruptions. These formations, geochemically distinct, are separated by thin silty or sandy horizons or by palaeosols. They include ‘compound pahoehoe flows’ and ‘simple flows’. The first type is almost exclusive of the lower formation, while the second type dominates the upper formation. The lava flows show clear evidence of endogenous growth or ‘inflation’. The characteristics of the volcanic pile suggest slow emplacement during sustained eruptive episodes and are compatible with a continental basaltic succession facies model.
Regulatable stiffness in relaxed airway smooth muscle: a target for asthma treatment?
Authors: Raqeeb Abdul , Jiao Yuekan , Syyong Harley T. , Paré Peter D. , Seow Chun Y.
Published: October 2011

The airway smooth muscle (ASM) layer within the airway wall modulates airway diameter and distensibility. Even in the relaxed state, the ASM layer possesses finite stiffness and limits the extent of airway distension by the radial force generated by parenchymal tethers and transmural pressure. Airway stiffness has often been attributed to passive elements, such as the extracellular matrix in the lamina reticularis, adventitia, and the smooth muscle layer that cannot be rapidly modulated by drug intervention such as ASM relaxation by β-agonists. In this study, we describe a calcium-sensitive component of ASM stiffness mediated through the Rho-kinase signaling pathway. The stiffness of ovine tracheal smooth muscle was assessed in the relaxed state under the following conditions: 1) in physiological saline solution (Krebs solution) with normal calcium concentration; 2) in calcium-free Krebs with 2 mM EGTA; 3) in Krebs with calcium entry blocker (SKF-96365); 4) in Krebs with myosin light chain kinase inhibitor (ML-7); and 5) in Krebs with Rho-kinase inhibitor (Y-27632). It was found that a substantial portion of the passive stiffness could be abolished when intracellular calcium was removed; this calcium-sensitive stiffness appeared to stem from intracellular source and was not sensitive to ML-7 inhibition of myosin light chain phosphorylation, but was sensitive to Y-27632 inhibition of Rho kinase. The results suggest that airway stiffness can be readily modulated by targeting the calcium-sensitive component of the passive stiffness within the muscle layer.
Endogenous BDNF regulates inhibitory synaptic transmission in the ventromedial nucleus of the hypothalamus
Authors: Jo Young-Hwan
Published: October 2011

Output from steroidogenic factor-1 (SF-1) neurons in the ventromedial nucleus of the hypothalamus (VMH) is anorexigenic. SF-1 neurons express brain-derived neurotrophic factor (BDNF) that contributes to the regulation of food intake and body weight. Here I show that regulation of GABAergic inputs onto SF-1 neurons by endogenous BDNF determines the anorexigenic outcome from the VMH. Single-cell RT-PCR analysis reveals that one-third of SF-1 neurons express BDNF and that only a subset of BDNF-expressing SF-1 neurons coexpresses the melanocortin receptor type 4. Whole cell patch-clamp analysis of SF-1 neurons in the VMH shows that exogenous BDNF significantly increases the frequency of spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs). This enhancement of GABA drive readily decreases the excitability of SF-1 neurons. However, treatment with BDNF has no significant effect on the frequency of TTX-independent GABAergic IPSCs. Moreover, TrkB receptors are not localized at the postsynaptic sites of GABAergic synapses on SF-1 neurons as there is no change in the amplitude of miniature IPSCs in the presence of BDNF. Dual patch-clamp recordings in mouse hypothalamic slices reveal that stimulation of one SF-1 neuron induces an increase in sIPSC frequency onto the neighboring SF-1 neuron. More importantly, this effect is blocked by a tyrosine kinase inhibitor. Hence, this increased GABA drive onto SF-1 neurons may, in part, explain the cellular mechanisms that mediate the anorexigenic effects of BDNF.
A decerebrate adult mouse model for examining the sensorimotor control of locomotion
Authors: Nakanishi Stan T. , Whelan Patrick J.
Published: October 2011

As wild-type and genetically modified mice are progressively becoming the predominant models for studying locomotor physiology, the technical ability to record sensory and motor components from adult mice, in vivo, are expected to contribute to a better understanding of sensorimotor spinal cord networks. Here, specific technical and surgical details are presented on how to produce an adult decerebrate mouse preparation that can reliably produce sustained bouts of stepping, in vivo, in the absence of anesthetic drugs. Data are presented demonstrating the ability of this preparation to produce stepping during treadmill locomotion, adaptability in its responses to changes in the treadmill speed, and left-right alternation. Furthermore, intracellular recordings from motoneurons and interneurons in the spinal cord are presented from preparations where muscle activity was blocked. Intraaxonal recordings are also presented demonstrating that individual afferents can be recorded using this preparation. These data demonstrate that the adult decerebrate mouse is a tractable preparation for the study of sensorimotor systems.
Differential neural correlates of reciprocal activation and cocontraction control in dorsal and ventral premotor cortices
Authors: Haruno Masahiko , Ganesh Gowrishankar , Burdet Etienne , Kawato Mitsuo
Published: October 2011

Efficient control of reciprocal activation and cocontraction of the muscles are critical to perform skillful actions with suitable force and impedance. However, it remains unclear how the brain controls force and impedance while recruiting the same set of muscles as actuators. Does control take place at the single muscle level leading to force and impedance, or are there higher-order centers dedicated to controlling force and impedance? We addressed this question using functional MRI during voluntary isometric wrist contractions with online electromyogram feedback. Comparison of the brain activity between the conditions requiring control of either wrist torque or cocontraction demonstrates that blood oxygen level-dependent activity in the caudo-dorsal premotor cortex (PMd) correlates well with torque, whereas the activity in the ventral premotor cortex (PMv) correlates well with the level of cocontraction. This suggests distinct roles of the PMd and PMv in the voluntary control of reciprocal activation and cocontraction of muscles, respectively.
Inhibitory responses inAplysiapleural sensory neurons act to block excitability, transmitter release, and PKC Apl II activation
Authors: Dunn Tyler W. , Farah Carole A. , Sossin Wayne S.
Published: October 2011

Expression of the 5-HT1Apl(a)receptor in Aplysia pleural sensory neurons inhibited 5-HT-mediated translocation of the novel PKC Apl II in sensory neurons and prevented PKC-dependent synaptic facilitation at sensory to motoneuron synapses ( Nagakura et al. 2010 ). We now demonstrate that the ability of inhibitory receptors to block PKC activation is a general feature of inhibitory receptors and is found after expression of the 5-HT1Apl(b)receptor and with activation of endogenous dopamine and FMRFamide receptors in sensory neurons. Pleural sensory neurons are heterogeneous for their inhibitory response to endogenous transmitters, with dopamine being the most prevalent, followed by FMRFamide, and only a small number of neurons with inhibitory responses to 5-HT. The inhibitory response is dominant, reduces membrane excitability and synaptic efficacy, and can reverse 5-HT facilitation at both naive and depressed synapses. Indeed, dopamine can reverse PKC translocation during the continued application of 5-HT. Reversal of translocation can also be seen after translocation mediated by an analog of diacylglycerol, suggesting inhibition is not through blockade of diacylglycerol production. The effects of inhibition on PKC translocation can be rescued by phosphatidic acid, consistent with the inhibitory response involving a reduction or block of production of this lipid. However, phosphatidic acid could not recover PKC-dependent synaptic facilitation due to an additional inhibitory effect on the non-L-type calcium flux linked to synaptic transmission. In summary, we find a novel mechanism downstream of inhibitory receptors linked to inhibition of PKC activation in Aplysia sensory neurons.
Synthesis of Nanocrystalline WC Single-Phase Refractory via Mechanical Milling
Authors: Razavi Mansour , Rahimipour Mohammad Reza , Yazdani-Rad Rahim
Published: October 2011

In this paper the possibility of production of nanocrystalline WC single-phase by mechanical milling has been investigated. The raw materials containing tungsten and carbon with WC as nucleation were milled in a planetary ball mill and sampled in different times. Studies showed that after 75 hours of milling the WC with W2C was produced and remained constant in higher milling time. Adding WC to raw materials at the beginning process leads to the fact that after 50 hours of milling only WC was synthesized without undesirable W2C phase. This material remained stable until higher times of milling too. From broadening of XRD peaks, the crystalline size in synthesized WC was estimated in nanometer scale which lower than the system containing primary WC, and it means that the strain in this system was lower than first system.
Static and Motional Feedthrough Capacitance of Flexural Microresonator
Authors: Chang Wen-Teng
Published: October 2011

The present paper evaluates the static and motional feedthrough capacitance of a silicon carbide-based flexural-mode microelectromechanical system resonator. The static feedthrough capacitance was measured by a network analyzer under atmospheric pressure. The motional feedthrough was obtained by introducing various values into the modeling circuit in order to fit the Bode plots measured under reduced pressure. The static feedthrough capacitance was 0.02 pF, whereas the motional feedthrough capacitance of an identical device was about 0.2 pF, which is one order of magnitude larger than the static feedthrough capacitance.
Selection Criteria for the Radical Treatment of Locally Advanced Rectal Cancer
Authors: Davies Mansel Leigh , Harris Dean , Davies Mark , Lucas Malcolm , Drew Peter , Beynon John
Published: October 2011

There are over 14,000 newly diagnosed rectal cancers per year in the United Kingdom of which between 50 and 64 percent are locally advanced (T3/T4) at presentation. Pelvic exenterative surgery was first described by Brunschwig in 1948 for advanced cervical cancer, but early series reported high morbidity and mortality. This approach was later applied to advanced primary rectal carcinomas with contemporary series reporting 5-year survival rates between 32 and 66 percent and to recurrent rectal carcinoma with survival rates of 22–42%. The Swansea Pelvic Oncology Group was established in 1999 and is involved in the assessment and management of advanced pelvic malignancies referred both regionally and UK wide. This paper will set out the selection, assessment, preparation, surgery, and outcomes from pelvic exenterative surgery for locally advanced primary rectal carcinomas.
Vortex Structures in a Rotating BEC Dark Matter Component
Authors: Zinner N. T.
Published: October 2011

We study the effects of a dark matter component that consists of bosonic particles with ultralight masses in the condensed state. We compare previous studies for both noninteracting condensates and with repulsive two-body terms and show consistency between the proposals. Furthermore, we explore the effects of rotation on a superfluid dark matter condensate, assuming that a vortex lattice is formed as seen in ultracold atomic gas experiments. The influence of such a lattice in virialization of gravitationally bound structures and on galactic rotation velocity curves is explored. With fine-tuning of the bosonic particle mass and the two-body repulsive interaction strength, we find that one can have substructure on rotation curves that resembles some observations in spiral galaxies. This occurs when the dark matter halo has an array of hollow cylinders. This can cause oscillatory behavior in the galactic rotation curves in similar fashion to the well-known effect of the spiral arms. We also consider how future experiments and numerical simulations with ultracold atomic gases could tell us more about such exotic dark matter proposals.
Explicit Bounds to Some New Gronwall‐Bellman‐Type Delay Integral Inequalities in Two Independent Variables on Time Scales
Authors: Meng Fanwei , Feng Qinghua , Zheng Bin
Published: October 2011

Some new Gronwall‐Bellman‐type delay integral inequalities in two independent variables on time scales are established, which provide a handy tool in the research of qualitative and quantitative properties of solutions of delay dynamic equations on time scales. The established inequalities generalize some of the results in the work of Zhang and Meng 2008, Pachpatte 2002, and Ma 2010.
Pseudoseptic Arthritis: A Case Series and Review of the Literature
Authors: Oppermann Brian P. , Cote Jonida K. , Morris Stephanie J. , Harrington Thomas
Published: October 2011

Purpose. Pseudoseptic arthritis is an acute inflammatory monoarthritis with a sterile synovial gram stain and culture. Pseudoseptic arthritis has been previously described in the literature in a variety of settings including rheumatoid arthritis and microcrystalline disease. Despite pseudoseptic arthritis being a described entity, there is little published data on this topic with no published reports since 1992.Methods. This paper was a retrospective chart review over a 20-year period that identified all rheumatology inpatient consultations at our tertiary rural hospital for pseudoseptic arthritis.Results. We identified 10 patients with pseudoseptic arthritis and presented 5 of those cases in this paper. Majority of these patients had known autoimmune inflammatory arthritis or microcrystalline inflammatory arthritis.Conclusion. Pseudoseptic arthritis is a syndrome that should be in the differential diagnosis with patients with long standing inflammatory condition who present with an acute monoarthritis with no known bacterial source for septic arthritis.
Enhancement of TGF-β Signaling Responses by the E3 Ubiquitin Ligase Arkadia Provides Tumor Suppression in Colorectal Cancer
Authors: Sharma Vikas , Antonacopoulou Anna G. , Tanaka Shinya , Panoutsopoulos Alexios A. , Bravou Vasiliki , Kalofonos Haralabos P. , Episkopou Vasso
Published: October 2011

TGF-β signaling provides tumor protection against colorectal cancer (CRC). Mechanisms that support its tumor-suppressive properties remain unclear. The ubiquitin ligase Arkadia/RNF111 enhances TGF-β signaling responses by targeting repressors of the pathway for degradation. The corepressors SnoN/Ski, critical substrates of Arkadia, complex with the activated TGF-β signaling effectors Smad2/3 (pSmad2/3) on the promoters of target genes and block their transcription. Arkadia degrades this complex including pSmad2/3 and unblocks the promoter. Here, we report that Arkadia is expressed highly in the mouse colonic epithelium. Heterozygous Akd+/− mice are normal but express less Arkadia. This leads to reduced expression of several TGF-β target genes, suggesting that normal levels of Arkadia are required for efficient signaling responses. Critically, Akd+/− mice exhibit increased susceptibility to azoxymethane/dextran sodium sulfate carcinogen–induced CRC, as they develop four-fold more tumors than wild-type mice. Akd+/− tumors also exhibit a more aggressive pathology, higher proliferation index, and reduced cytostasis. Therefore, Arkadia functions as a tumor suppressor whose peak expression is required to suppress CRC development and progression. The accumulation of nuclear SnoN and pSmad2, along with the downregulation of TGF-β target genes observed in Akd+/− colon and tumors, suggest that tumor-suppressing properties of Arkadia are mediated by its ability to derepress TGF-β signaling. Consistent with this likelihood, we identified mutations in primary colorectal tumors from human patients that reduce Arkadia function and are associated with the accumulation of nuclear SNON. Collectively, our findings reveal that Arkadia enhances TGF-β signaling responses and supports its tumor-suppressing properties in CRC. Cancer Res; 71(20); 6438–49. ©2011 AACR.
EGFR Protein Expression in Non–Small Cell Lung Cancer Predicts Response to an EGFR Tyrosine Kinase Inhibitor—A Novel Antibody for Immunohistochemistry or AQUA Technology
Authors: Mascaux Celine , Wynes Murry W. , Kato Yasufumi , Tran Cindy , Asuncion Bernadette Reyna , Zhao Jason M. , Gustavson Mark , Ranger-Moore Jim , Gaire Fabien , Matsubayashi Jun , Nagao Toshitaka , Yoshida Koichi , Ohira Tatuso , Ikeda Norihiko , Hirsch Fred R.
Published: October 2011

Introduction: Epidermal growth factor receptor (EGFR) protein expression in non–small cell lung cancer (NSCLC) is not recommended for predicting response to EGFR tyrosine kinase inhibitors (TKI) due to conflicting results, all using antibodies detecting EGFR external domain (ED). We tested the predictive value of EGFR protein expression for response to an EGFR TKI with an antibody that detects the intracellular domain (ID) and compared fluorescence-based Automated QUantitative Analysis (AQUA) technology to immunohistochemistry (IHC).

Methods: Specimens from 98 gefitinib-treated NSCLC Japanese patients were evaluated by IHC (n = 98 of 98) and AQUA technology (n = 70 of 98). EGFR ID (5B7)- and ED-specific antibodies (3C6 and 31G7) were compared.

Results: EGFR expression evaluated with 5B7 was significantly higher in responders versus nonresponders to gefitinib both with IHC and with AQUA. ED-specific antibodies did not significantly predict response. Using AQUA and ID-specific antibody resulted in the best prediction performance with a positive and negative predictive value (PPV/NPV) for responders of 50% and 87%, respectively. EGFR expression with ID-specific antibody and AQUA also predicted responders in EGFR-mutated patients. Increased EGFR expression with the ID antibody is associated with increased median progression free survival (PFS; 11.7 months vs. 5.0, log rank, P = 0.034) and overall survival (OS; 38.6 vs. 14.9, P = 0.040) from gefitinib therapy.

Conclusions: EGFR protein expression using an ID-specific antibody specifically predicts response to gefitinib in NSCLC patients, including in EGFR-mutated patients, and increased PFS/OS from gefitinib. These data suggest that the choice of diagnostic antibody and methodology matters to predict response and outcome to specific therapies. The potential clinical application needs further validation. Clin Cancer Res; 17(24); 7796–807. ©2011 AACR.
Phase I Trial of ALT-801, an Interleukin-2/T-Cell Receptor Fusion Protein Targeting p53 (aa264–272)/HLA-A*0201 Complex, in Patients with Advanced Malignancies
Authors: Fishman Mayer N. , Thompson John A. , Pennock Gregory K. , Gonzalez Rene , Diez Luz M. , Daud Adil I. , Weber Jeffery S. , Huang Bee Y. , Tang Shamay , Rhode Peter R. , Wong Hing C.
Published: October 2011

Purpose: ALT-801 is a bifunctional fusion protein comprising interleukin-2 (IL-2) linked to a soluble, single-chain T-cell receptor domain that recognizes a peptide epitope (aa264–272) of the human p53 antigen displayed on cancer cells in the context of HLA-A*0201 (p53+/HLA-A*0201). We evaluated the safety, pharmacokinetics, and pharmacodynamics of ALT-801 in p53+/HLA-A*0201 patients with metastatic malignancies.

Experimental Design: p53+/HLA-A*0201 patients were treated with ALT-801 on a schedule of four daily 15-minute intravenous infusions, then 10 days rest and four more daily infusions. Cohorts of patients were treated at 0.015, 0.040, and 0.080 mg/kg/dose.

Results: Four, 16, and 6 patients were treated at the 0.015, 0.04, and 0.08 mg/kg cohorts, respectively. Two dose-limiting toxicities (a grade 4 transient thrombocytopenia and a myocardial infarction) in the 0.08 mg/kg cohort established the maximum tolerated dose (MTD) at 0.04 mg/kg. Patients treated at the MTD experienced toxicities similar to those associated with high-dose IL-2 but of lesser severity. The serum half-life of ALT-801 was 4 hours and ALT-801 serum recovery was as expected based on the dose administered. ALT-801 treatment induced an increase of serum IFN-γ but not TNF-α. Response assessment showed 10 subjects with stable disease at at least 11 weeks, and in one who had melanoma metastasis, there is an ongoing complete absence of identifiable disease after resection of radiographically identified lesions.

Conclusion: This first-in-man study defines an ALT-801 regimen that can be administered safely and is associated with immunologic changes of potential antitumor relevance. Clin Cancer Res; 17(24); 7765–75. ©2011 AACR.
Incidence and Dynamics of Thyroid Dysfunction and Thyroid Autoimmunity in Girls with Turner’s Syndrome: A Long-Term Follow-Up Study
Authors: Gawlik Aneta , Gawlik Tomasz , Januszek-Trzciakowska Aleksandra , Patel Hemangini , Malecka-Tendera Ewa
Published: October 2011

Objective: Clinical studies suggest that the thyroid autoantibodies and/or hypothyroidism are not present in Turner’s syndrome (TS) patients before the age of 8 years and are more frequent in patients with the X isochromosome. The aim of the study was to analyze the dynamics of thyroid dysfunction in girls with TS. Design: 86 TS patients with a median age of 10.6 years were followed for 4.6 ± 3.0 years. Outcomes: The prevalence of thyroid abnormalities increased from 25.5 to 50% during the follow-up. Finally, 31 (36%) patients had positive thyroid autoantibodies and 27 (31.4%) had subclinical hypothyroidism. Hashimoto’s thyroiditis was diagnosed in 15 patients. Median age of developing thyroid antibodies and subclinical hypothyroidism was 14.1 and 14.8 years, respectively. The youngest hypothyroid patient was 1.8 years old and the youngest girl with positive anti-thyroid antibodies was 5.5 years old. Autoantibodies appeared mainly after the age of 13. The risk of developing subclinical hypothyroidism was greatest between 12 and 14 years of age. The prevalence of thyroid abnormalities was not related to the karyotype. Conclusions: Thyroid autoimmunity and dysfunctions in TS may start early, their prevalence increases with age, independently of karyotype and without any clinical symptoms and signs.
Cassia angustifolia Extract Is Not Hepatotoxic in an in vitro and in vivo Study
Authors: Vitalone A. , Di Giacomo S. , Di Sotto A. , Franchitto A. , Mammola C.L. , Mariani P. , Mastrangelo S. , Mazzanti G.
Published: October 2011

Background:Cassia angustifolia L. (senna) is traditionally used as a laxative. Its major components are sennosides that are responsible for the laxative effect. Senna is recommended for the short-term treatment of acute constipation. Nevertheless people use its preparations as self-medication, often for long periods, to treat chronic constipation thus exposing themselves to adverse reactions. Most reactions were associated with hepatotoxicity. Aims: The present study was aimed to evaluate the toxicity of a C. angustifolia leafextract (standardized at 60% of sennosides) on rat liver cells and the long-term effects on liver functions, in Wistar rats. Methods: Cytotoxicity was assessed in a buffalo normal rat liver cell line (BRL-3A) by the trypan blue assay and the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction test. In vivo effects were observed after oral administration of the extract for 4 or 8 weeks at doses of 12 and 58 mg/kg/day. At the end of treatment, animals were sacrificed, the postmortem examination was performed and serum was used for biochemical analysis. Liver samples were used for histomorphological and immunohistochemical examination along with the determination of oxidative stress parameters. Results and Conclusion: In BRL-3A cells, the extract was cytotoxic at concentrations that appear largely higher than those attainable in humans. In Wistar rats, the extract did not induce any significant change in all of the parameters tested. In summary, the present study indicates a lack of hepatotoxicity of senna at doses higher than those generally used in humans.