bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcium‐dependent regulation of climbing fibre synapse elimination during postnatal cerebellar development
Authors: Kano Masanobu , Nakayama Hisako , Hashimoto Kouichi , Kitamura Kazuo , Sakimura Kenji , Watanabe Masahiko
Published: January 2013

Abstract  Functional neural circuit formation during postnatal development involves massive elimination of early‐formed redundant synapses and strengthening of necessary synaptic connections. In the cerebellum, one‐to‐one connection from a climbing fibre (CF) to a Purkinje cell (PC) is established through four distinct phases: (1) strengthening of a single CF among multiple CFs in each PC at postnatal age P3–P7 days, (2) translocation of a single strengthened CF to PC dendrites from around P9, (3) early‐phase (P7 to around P11) and (4) late‐phase (around P12–P17) elimination of weak CF synapses from PC somata. Mice with PC‐selective deletion of the P/Q‐type voltage‐dependent Ca2+ channel (VDCC) exhibit severe defects in strengthening of single CFs, dendritic translocation of single CFs and CF elimination from P7. In contrast, mice with a mutation of a single allele for the GABA synthesizing enzyme GAD67 show selective impairment of CF elimination from P10. Electrophysiological and Ca2+ imaging data suggest that GABAA receptor‐mediated inhibition onto PC somata from putative basket cells influences CF‐induced Ca2+ transients and regulates elimination of redundant CF synapses from PC somata at P10–P16. Thus, regulation of Ca2+ influx to PCs through VDCCs is crucial for the four phases of CF synapse elimination during postnatal development.
Prospects for Implementation of Thermoelectric Generators as Waste Heat Recovery Systems in Class 8 Truck Applications
Authors: Schock Harold , Brereton Giles , Case Eldon , D'Angelo Jonathan , Hogan Tim , Lyle Matt , Maloney Ryan , Moran Kevin , Novak James , Nelson Christopher , Panayi Andreas , Ruckle Trevor , Sakamoto Jeffery , Shih Tom , Timm Ed , Zhang Long , Zhu George
Published: January 2013

With the rising cost of fuel and increasing demand for clean energy, solid-state thermoelectric (TE) devices are an attractive option for reducing fuel consumption and CO2 emissions. Although they are reliable energy converters, there are several barriers that have limited their implementation into wide market acceptance for automotive applications. These barriers include: the unsuitability of conventional thermoelectric materials for the automotive waste heat recovery temperature range; the rarity and toxicity of some otherwise suitable materials; and the limited ability to mass-manufacture thermoelectric devices from certain materials. One class of material that has demonstrated significant promise in the waste heat recovery temperature range is skutterudites. These materials have little toxicity, are relatively abundant, and have been investigated by NASA-JPL for the past twenty years as possible thermoelectric materials for space applications. In a recent collaboration between Michigan State University (MSU) and NASA-JPL, the first skutterudite-based 100 W thermoelectric generator (TEG) was constructed. In this paper, we will describe the efforts that have been directed towards: (a) enhancing the technology-readiness level of skutterudites to facilitate mass manufacturing similar to that of Bi2Te3, (b) optimizing skutterudites to improve thermal-to-electric conversion efficiencies for class 8 truck applications, and (c) describing how temperature cycling, oxidation, sublimation, and other barriers to wide market acceptance must be managed. To obtain the maximum performance from these devices, effective heat transfer systems need to be developed for integration of thermoelectric modules into practical generators.
Ca(NO3)2—NaNO3—KNO3 Molten Salt Mixtures for Direct Thermal Energy Storage Systems in Parabolic Trough Plants
Authors: Gomez Judith C. , Calvet Nicolas , Starace Anne K. , Glatzmaier Greg C.
Published: January 2013

Molten salts are currently the only thermal energy storage media operating with multiple hours of energy capacity in commercial concentrated solar power (CSP) plants. Thermal energy is stored by sensible heat in the liquid phase. A lower melting point in the range of 60–120 °C and a decomposition temperature above 500 °C are desired because such a fluid would enhance the overall efficiency of the plants by utilizing less energy to keep the salt in the liquid state and by producing superheated steam at higher temperatures in the Rankine cycle. One promising candidate is a multicomponent NaNO3—KNO3—Ca(NO3)2 molten salt. Different compositions have been reported in literature as the best formulation for CSP plants based on melting temperature. In this paper, the National Renewable Energy Laboratory (NREL) presents the handling, preparation, thermal properties, and characterization of different compositions for this ternary nitrate salt, and comparisons are drawn accordingly. This system has a high tendency to form supercooled liquids with high viscosity that undergo glass formation during cooling. When the proportion of Ca(NO3)2 decreases, the formulations become more thermally stable, the viscosity goes down, and the system increases its degree of crystalline solidification. Differential scanning calorimetry (DSC) tests showed the presence of a ternary eutectoid solid–solid invariant reaction at around 100 °C. The eutectic invariant reaction was resolved between 120 and 133 °C as reported in the literature. Based on DSC and viscosity results, the best composition would seem to be 36 wt. % Ca(NO3)2—16 wt. % NaNO3—48 wt. % KNO3, which showed a low solidification point.
A Machining Science Approach to Dental Cutting of Glass Ceramics Using an Electric Handpiece and Diamond Burs
Authors: Song Xiao-Fei , Peng Jian-Hui , Yin Ling , Lin Bin
Published: January 2013

Dental cutting using handpieces has been the art of dentists in restorative dentistry. This paper reports on the scientific approach of dental cutting of two dental ceramics using a high-speed electric handpiece and coarse diamond burs in simulated clinical conditions. Cutting characteristics (forces, force ratios, specific removal energy, surface roughness, and morphology) of feldspar and leucite glass ceramics were investigated as functions of the specific material removal rate, Qw and the maximum undeformed chip thickness, hmax. The results show that up and down cutting remarkably affected cutting forces, force ratios, and specific cutting energy but did not affect surface roughness and morphology. Down cutting resulted in much lower tangential and normal forces, and specific cutting energy, but higher force ratios. The cutting forces increased with the Qw and hmax while the specific cutting energy decreased with the Qw and hmax. The force ratios and surface roughness showed no correlations with the Qw and hmax. Surface morphology indicates that the machined surfaces contained plastically flowed and brittle fracture regions at any Qw and hmax. Better surface quality was achieved at the lower Qw and the smaller hmax. These results provide fundamental data and a scientific understanding of ceramic cutting using electric dental handpieces in dental practice.
Characterization of Flow-Magnetic Field Interactions in Magneto-Hydrodynamic Turbulence
Authors: Richard Jacques C. , Kumar Gaurav , Kalmár-Nagy Tamás , Girimaji Sharath S.
Published: January 2013

We examine the complex nonlinear flow-magnetic field dynamics in magneto-hydrodynamic (MHD) turbulence. Using direct numerical simulations (DNS), we investigate the dynamical interactions subject to the influence of a uniform applied background magnetic field. The initial magnetic and kinetic Reynolds numbers (based on Taylor microscale) are 45 and there are no initial magnetic field fluctuations. The sum total of turbulent magnetic and kinetic energies decays monotonically. With time, the turbulent magnetic fluctuations grow by extracting energy from velocity fluctuations. Expectedly, the distribution of energy between kinetic and magnetic fluctuations exhibits large periodic oscillations from the equipartition state due to Alfvén waves. We perform a detailed analysis of the flow-magnetic field coupling and posit a simple model for the energy interchange. Such dynamical analysis can provide the insight required for turbulence control and closure modeling strategies.
Tooth Contact Analysis and Manufacture on Multitasking Machine of Large-Sized Straight Bevel Gears With Equi-Depth Teeth
Authors: Tsuji Isamu , Kawasaki Kazumasa , Gunbara Hiroshi , Houjoh Haruo , Matsumura Shigeki
Published: January 2013

Straight bevel gears are widely used in the plant of large-sized power generation when the gears have large size. The purpose of this study is to manufacture the large-sized straight bevel gears with equi-depth teeth on a multitasking machine. The manufacturing method has the advantages of arbitrary modification of the tooth surface and machining of the part without the tooth surface. For this study, first, the mathematical model of straight bevel gears by complementary crown gears considering manufacture on multitasking machine is proposed, and the tooth contact pattern and transmission errors of these straight bevel gears with modified tooth surfaces are analyzed in order to clarify the meshing and contact of these gears. Next, the numerical coordinates on the tooth surfaces of the bevel gears are calculated and the tooth profiles are modeled using a 3D-Computer-Aided Design (CAD) system. Five-axis control machines were utilized. The gear-work was machined by a swarf cutting using a coated carbide end mill. After rough cutting, the gear-work was heat-treated, and it was finished based on a Computer-Aided Manufacturing (CAM) process through the calculated numerical coordinates. The pinion was also machined similarly. The real tooth surfaces were measured using a coordinate measuring machine and the tooth flank form errors were detected using the measured coordinates. As a result, the obtained tooth flank form errors were small. In addition, the tooth contact pattern of the manufactured large-sized straight bevel gears was compared with those of tooth contact analysis. The data showed good agreement.
System-Level Biomechanical Approach for the Evaluation of Term and Preterm Pregnancy Maintenance
Authors: Mahmoud Hussam , Wagoner Johnson Amy , Chien Edward K. , Poellmann Michael J. , McFarlin Barbara
Published: January 2013

Preterm birth is the primary contributor to perinatal morbidity and mortality, with those born prior to 32 weeks disproportionately contributing compared to those born at 32–37 weeks. Outcomes for babies born prematurely can be devastating. Parturition is recognized as a mechanical process that involves the two processes that are required to initiate labor: rhythmic myometrial contractions and cervical remodeling with subsequent dilation. Studies of parturition tend to separate these two processes rather than evaluate them as a unified system. The mechanical property characterization of the cervix has been primarily performed on isolated cervical tissue, with an implied understanding of the contribution from the uterine corpus. Few studies have evaluated the function of the uterine corpus in the absence of myometrial contractions or in relationship to retaining the fetus. Therefore, the cervical-uterine interaction has largely been neglected in the literature. We suggest that a system-level biomechanical approach is needed to understand pregnancy maintenance. To that end, this paper has two main goals. One goal is to highlight the gaps in current knowledge that need to be addressed in order to develop any comprehensive and clinically relevant models of the system. The second goal is to illustrate the utility of finite element models in understanding pregnancy maintenance of the cervical-uterine system. The paper targets an audience that includes the reproductive biologist/clinician and the engineer/physical scientist interested in biomechanics and the system level behavior of tissues.
Hydrodynamic Interaction Between a Platelet and an Erythrocyte: Effect of Erythrocyte Deformability, Dynamics, and Wall Proximity
Authors: Vahidkhah Koohyar , Diamond Scott L. , Bagchi Prosenjit
Published: January 2013

We present three-dimensional numerical simulations of hydrodynamic interaction between a red blood cell (RBC) and a platelet in a wall-bounded shear flow. The dynamics and large deformation of the RBC are fully resolved in the simulations using a front-tracking method. The objective is to quantify the influence of tank treading and tumbling dynamics of the RBC, and the presence of a bounding wall on the deflection of platelet trajectories. We observe two types of interaction: A crossing event in which the platelet comes in close proximity to the RBC, rolls over it, and continues to move in the same direction; and a turning event in which the platelet turns away before coming close to the RBC. The crossing events occur when the initial lateral separation between the cells is above a critical separation, and the turning events occur when it is below the critical separation. The critical lateral separation is found to be higher during the tumbling motion than that during the tank treading. When the RBC is flowing closer to the wall than the platelet, the critical separation increases by several fold, implying the turning events have higher probability to occur than the crossing events. On the contrary, if the platelet is flowing closer to the wall than the RBC, the critical separation decreases by several folds, implying the crossing events are likely to occur. Based on the numerical results, we propose a mechanism of continual platelet drift from the RBC-rich region of the vessel towards the wall by a succession of turning and crossing events. The trajectory deflection in the crossing events is found to depend nonmonotonically on the initial lateral separation, unlike the monotonic trend observed in tracer particle deflection and in deformable sphere-sphere collision. This nonmonotonic trend is shown to be a consequence of the deformation of the RBC caused by the platelet upon collision. An estimation of the platelet diffusion coefficient yields values that are similar to those reported in experiments and computer simulations with multicellular suspension.
Rectus Femoris Knee Muscle Moment Arms Measured in Vivo During Dynamic Motion With Real-Time Magnetic Resonance Imaging
Authors: Fiorentino Niccolo M. , Lin Jonathan S. , Ridder Kathryn B. , Guttman Michael A. , McVeigh Elliot R. , Blemker Silvia S.
Published: January 2013

Moment arms represent a muscle's ability to generate a moment about a joint for a given muscle force. The goal of this study was to develop a method to measure muscle moment arms in vivo over a large range of motion using real-time magnetic resonance (MR) imaging. Rectus femoris muscle-tendon lengths and knee joint angles of healthy subjects (N = 4) were measured during dynamic knee joint flexion and extension in a large-bore magnetic resonance imaging (MRI) scanner. Muscle-tendon moment arms were determined at the knee using the tendon-excursion method by differentiating measured muscle-tendon length with respect to joint angle. Rectus femoris moment arms were averaged across a group of healthy subjects and were found to vary similarly during knee joint flexion (mean: 3.0 (SD 0.5) cm, maximum: 3.5 cm) and extension (mean: 2.8 (SD 0.4) cm, maximum: 3.6 cm). These moment arms compare favorably with previously published dynamic tendon-excursion measurements in cadaveric specimens but were relatively smaller than moment arms from center-of-rotation studies. The method presented here provides a new approach to measure muscle-tendon moment arms in vivo and has the potential to be a powerful resource for characterizing musculoskeletal geometry during dynamic joint motion.
Gated photon correlation spectroscopy for acoustical particle velocity measurements in free-field conditions
Authors: Koukoulas Triantafillos , Piper Ben , Theobald Pete
Published: January 2013

The measurement of acoustic pressure at a point in space using optical methods has been the subject of extensive research in airborne acoustics over the last four decades. The main driver is to reliably establish the acoustic pascal, thus allowing the calibration of microphones with standard and non-standard dimensions to be realized in an absolute and direct manner. However, the research work so far has mostly been limited to standing wave tubes. This Letter reports on the development of an optical system capable of measuring acoustic particle velocities in free-field conditions; agreement within less than 0.6 dB was obtained with standard microphone measurements during these initial experiments.
IKK Goes BAD
Authors: Foley John F.
Published: January 2013

The IKK complex targets the proapoptotic protein BAD to inhibit TNF-induced apoptosis independently of nuclear factor κB signaling.
Balancing the Humoral Response
Authors: Ferrarelli Leslie K.
Published: January 2013

The receptor PD-1 inhibits follicular regulatory T cell–mediated suppression of antibody production.
Synergistic Effects of Amiodarone and Fluconazole on Candida tropicalis Resistant to Fluconazole
Authors: da Silva Cecília Rocha , de Andrade Neto João Batista , Sidrim José Júlio Costa , Ângelo Maria Rozzelê Ferreira , Magalhães Hemerson Iury Ferreira , Cavalcanti Bruno Coêlho , Brilhante Raimunda Sâmia Nogueira , Macedo Danielle Silveira , de Moraes Manoel Odorico , Lobo Marina Duarte Pinto , Grangeiro Thalles Barbosa , Nobre Júnior Hélio Vitoriano
Published: January 2013

There have recently been significant increases in the prevalence of systemic invasive fungal infections. However, the number of antifungal drugs on the market is limited in comparison to the number of available antibacterial drugs. This fact, coupled with the increased frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. Combination drug therapies have become one of the most widely used and effective strategies to alleviate this problem. Amiodarone (AMD) is classically used for the treatment of atrial fibrillation and is the drug of choice for patients with arrhythmia. Recent studies have shown broad antifungal activity of the drug when administered in combination with fluconazole (FLC). In the present study, we induced resistance to fluconazole in six strains of
Candida tropicalis
and evaluated potential synergism between fluconazole and amiodarone. The evaluation of drug interaction was determined by calculating the fractional inhibitory concentration and by performing flow cytometry. We conclude that amiodarone, when administered in combination with fluconazole, exhibits activity against strains of
C. tropicalis
that are resistant to fluconazole, which most likely occurs via changes in the integrity of the yeast cell membrane and the generation of oxidative stress, mitochondrial dysfunction, and DNA damage that could lead to cell death by apoptosis.
Contribution of Topoisomerase IV Mutation to Quinolone Resistance in Mycoplasma genitalium
Authors: Yamaguchi Yuko , Takei Masaya , Kishii Ryuta , Yasuda Mitsuru , Deguchi Takashi
Published: January 2013

The mechanism of quinolone resistance in
Mycoplasma genitalium
remains poorly understood due to difficulties with
in vitro
culture, especially of clinical isolates. In this study, to confirm the association between mutations in topoisomerases and antimicrobial susceptibilities to quinolones, ciprofloxacin-resistant mutant strains were selected using the cultivable type strain ATCC 33530. Sequence analysis revealed that the mutant strains harbored mutations in topoisomerase IV: Gly81Cys in ParC, Pro261Thr in ParC, or Asn466Lys in ParE. The MICs of all quinolones tested against the mutant strains were 2- to 16-fold higher than those against the wild-type strain. No cross-resistance was observed with macrolides or tetracyclines. We determined the inhibitory activities of quinolones against DNA gyrase and topoisomerase IV in order to investigate the correlation between antimicrobial susceptibility and inhibitory activity against the target enzymes, considered the primary targets of quinolones. Furthermore, using enzymatic analysis, we confirmed that Gly81Cys in the ParC quinolone resistance-determining region (QRDR) contributed to quinolone resistance. This is the first study to isolate quinolone-resistant mutant strains of
M. genitalium
harboring substitutions in the
parC
or
parE
gene
in vitro
and to measure the inhibitory activities against the purified topoisomerases of
M. genitalium
.
Blood, Tissue, and Intracellular Concentrations of Azithromycin during and after End of Therapy
Authors: Matzneller P. , Krasniqi S. , Kinzig M. , Sörgel F. , Hüttner S. , Lackner E. , Müller M. , Zeitlinger M.
Published: January 2013

Although azithromycin is extensively used in the treatment of respiratory tract infections as well as skin and skin-related infections, pharmacokinetics of azithromycin in extracellular space fluid of soft tissues, i.e., one of its therapeutic target sites, are not yet fully elucidated. In this study, azithromycin concentration-time profiles in extracellular space of muscle and subcutaneous adipose tissue, but also in plasma and white blood cells, were determined at days 1 and 3 of treatment as well as 2 and 7 days after the end of treatment. Of all compartments, azithromycin concentrations were highest in white blood cells, attesting for intracellular accumulation. However, azithromycin concentrations in both soft tissues were markedly lower than in plasma both during and after treatment. Calculation of the area under the concentration-time curve from 0 to 24 h (AUC
0–24
)/MIC
90
ratios for selected pathogens suggests that azithromycin concentrations measured in the present study are subinhibitory at all time points in both soft tissues and at the large majority of observed time points in plasma. Hence, it might be speculated that azithromycin's clinical efficacy relies not only on elevated intracellular concentrations but possibly also on its known pleotropic effects, including immunomodulation and influence on bacterial virulence factors. However, prolonged subinhibitory azithromycin concentrations at the target site, as observed in the present study, might favor the emergence of bacterial resistance and should therefore be considered with concern. In conclusion, this study has added important information to the pharmacokinetic profile of the widely used antibiotic drug azithromycin and evidentiates the need for further research on its potential for induction of bacterial resistance.
Pharmacokinetic and Pharmacodynamic Evaluation of P-873 versus Klebsiella pneumoniae in a Neutropenic Murine Thigh Infection Model
Authors: Lamb Lucinda M. , Crandon Jared L. , Nicolau David P.
Published: January 2013

P-873 is a novel compound in the RX-04 pyrrolocytosine series of protein synthesis inhibitors currently under development by Rib-X Pharmaceuticals. We evaluated the pharmacodynamic and pharmacokinetic properties of this compound against
Klebsiella pneumoniae
using a murine neutropenic thigh infection model. P-873 demonstrated potent and rapid
in vivo
activity against this organism with enhanced penetration and duration of exposure in thigh tissue.
Target Gene Sequencing To Define the Susceptibility of Neisseria meningitidis to Ciprofloxacin
Authors: Hong Eva , Thulin Hedberg Sara , Abad Raquel , Fazio Cecilia , Enríquez Rocío , Deghmane Ala-Eddine , Jolley Keith A. , Stefanelli Paola , Unemo Magnus , Vazquez Julio A. , Veyrier Frédéric J. , Taha Muhamed-Kheir
Published: January 2013

Meningococcal
gyrA
gene sequence data, MICs, and mouse infection were used to define the ciprofloxacin breakpoint for
Neisseria meningitidis
. Residue T91 or D95 of GyrA was altered in all meningococcal isolates with MICs of ≥0.064 μg/ml but not among isolates with MICs of ≤0.032 μg/ml. Experimental infection of ciprofloxacin-treated mice showed slower bacterial clearance when GyrA was altered. These data suggest a MIC of ≥0.064 μg/ml as the ciprofloxacin breakpoint for meningococci and argue for the molecular detection of ciprofloxacin resistance.
Pharmacokinetics, Metabolism, and Excretion of the Antiviral Drug Arbidol in Humans
Authors: Deng Pan , Zhong Dafang , Yu Kate , Zhang Yifan , Wang Ting , Chen Xiaoyan
Published: January 2013

Arbidol is a broad-spectrum antiviral drug that is used clinically to treat influenza. In this study, the pharmacokinetics, metabolism, and excretion of arbidol were investigated in healthy male Chinese volunteers after a single oral administration of 200 mg of arbidol hydrochloride. A total of 33 arbidol metabolites were identified in human plasma, urine, and feces. The principal biotransformation pathways included sulfoxidation, dimethylamine
N
-demethylation, glucuronidation, and sulfate conjugation. The major drug-related component in the plasma was sulfinylarbidol (M6-1), followed by unmetabolized arbidol,
N
-demethylsulfinylarbidol (M5), and sulfonylarbidol (M8). The exposures of M5, M6-1, and M8, as determined by the metabolite-to-parent area under the plasma concentration-time curve from 0 to
t
(AUC

0-
t

) ratio, were 0.9 ± 0.3, 11.5 ± 3.6, and 0.5 ± 0.2, respectively. In human urine, glucuronide and sulfate conjugates were detected as the major metabolites, accounting for 6.3% of the dose excreted within 0 to 96 h after drug administration. The fecal specimens mainly contained the unchanged arbidol, accounting for 32.4% of the dose. Microsomal incubation experiments demonstrated that the liver and intestines were the major organs that metabolize arbidol in humans. CYP3A4 was the major isoform involved in arbidol metabolism, whereas the other P450s and flavin-containing monooxygenases (FMOs) played minor roles. These results indicated possible drug interactions between arbidol and CYP3A4 inhibitors and inducers. Further investigations are needed to understand the importance of M6-1 in the efficacy and safety of arbidol, because of its high plasma exposure and long elimination half-life (25.0 h).
Evaluation of the Effect of a Supratherapeutic Dose of Intravenous Ceftaroline Fosamil on the Corrected QT Interval
Authors: Riccobene Todd A. , Rekeda Ludmyla , Rank Douglas , Llorens Lily
Published: January 2013

A randomized, double-blind, placebo-controlled, 3-period crossover study was conducted in 54 healthy adults to assess the effect of ceftaroline fosamil on the corrected QT (QTc) interval. The QT interval, corrected for heart rate using an individual correction formula (QTcIb), was determined predose and at 1, 1.25, 1.5, 2, 4, 8, 12, and 24.5 h after intravenous dosing with a supratherapeutic dose (1,500 mg) of ceftaroline fosamil, 400 mg moxifloxacin (positive control), and placebo. The pharmacokinetic profile of ceftaroline was also evaluated. At each time point following ceftaroline fosamil administration, the upper limit of the 90% confidence interval (CI) for the placebo-corrected change from predose baseline in QTcIb (ΔΔQTcIb) was below 10 ms (maximum, 3.4 ms at 1.5 h after dosing), indicating an absence of clinically meaningful QTc increase. The lower limit of the 90% CI of ΔΔQTcIb for moxifloxacin versus placebo was greater than 5 ms at 5 time points (maximum, 12.8 ms at 1 h after dosing), demonstrating assay sensitivity. There was no apparent correlation between ceftaroline plasma concentrations and ΔΔQTcIb. The supratherapeutic dose of ceftaroline fosamil (1,500 mg) resulted in substantially greater systemic exposure to ceftaroline than previously observed with standard therapeutic doses. Ceftaroline fosamil was well tolerated after a single 1,500-mg intravenous dose, and no clinically meaningful abnormalities in laboratory values or vital signs were observed.
Berardinelli–Seip syndrome: highlight of treatment challenge
Authors: Ferraria Nélia , Pedrosa Cristina , Amaral Daniela , Lopes Lurdes
Published: January 2013

Berardinelli–Seip congenital lipodystrophy (BSCL) syndrome is a rare autosomal-recessive disease characterised by lipoatrophy and associated with deregulations of glycidic and lipid metabolism. We report three BSCL cases with its typical clinical picture and complications. Clinically, they all show marked atrophy of adipose tissue, acromegaly, acanthosis nigricans and tall stature. Two cases present attention deficit hyperactivity and developmental learning disorders; another patient has hypertrophic myocardiopathy and polycystic ovary syndrome. In all the cases AGPAT2 was the identified mutation. All the cases present hypertriglyceridemia. One case has developed hyperinsulinism controlled with metformin and another case already has type 2 diabetes with a difficult clinical control. There is no curative treatment and the current treatment options are based only on symptomatic control of the complications. Recently, published studies showed that leptin-replacement therapy appears a promising tool in the metabolic correction of BSCL complications, highlighting the importance of further investigations in BSCL treatment.
A previously unreported serious adverse event during balloon sinuplasty
Authors: Hughes Nadine , Bewick Jessica , Van Der Most Renee , O'Connell Mike
Published: January 2013

Balloon sinuplasty is considered as a minimally invasive procedure for the treatment of chronic rhinosinusitis. In this case report we describe how a patient undergoing balloon sinuplasty sustained an intraoperative cardiac arrest with no cardiac history. Postoperative investigations were all normal. The patient was discharged on the first postoperative day and further outpatient tests were normal. We postulate that this event occurred due to profound vagal stimulation either on instrumentation of the maxillary mucosa or when the orbit was accidently breached during instrumentation of the right frontal recess. The authors conclude that balloon sinuplasty, despite being minimally invasive surgery, should be performed under the supervision of an anaesthesiologist with the ability of cardiac monitoring and immediate treatment because of possible arrhythmias.
Intraoral lipoma: a rare clinical entity
Authors: Agarwal Rashmi , Kumar Vikas , Kaushal Ambrish , Singh Rajeev Kumar
Published: January 2013

Lipoma is a painless soft tissue tumour of the mesenchymal origin, which is slow growing and well circumscribed. The occurrence of lipoma is rare in the oral cavity (1–4%); however, the frequency is much higher in the head and neck region. The tumour is mostly present in the buccal mucosa, lips, tongue, palate, buccal sulcus and floor of the mouth. Sometimes the tumour becomes large enough to cause difficulty in speech and mastication. Histologically, lipoma is composed of mature fat cells, surrounded by normal fat. We present two cases of intraoral lipoma in two female patients.
Cardiac tumour masquerades as mid-life (menopause) event
Authors: Rosser Gareth J , Goode Emily F , Godazgar Faezah , Dubrey Simon William
Published: January 2013

Atrial myxomas are the most common primary cardiac tumours encountered. Their detection may be incidental, owing to embolic events, intracardiac obstructive features or in some cases, non-specific constitutional symptoms. We describe a middle-aged woman attributing constitutional symptoms to menopause, but later determined to be due to an atrial myxoma.
EGFR status in oral squamous cell carcinoma: comparing immunohistochemistry, FISH and CISH detection in a case series study
Authors: Bernardes Vanessa Fátima , Gleber-Netto Frederico Omar , Sousa Sílvia Ferreira de , Rocha Rafael Malagoli , Aguiar Maria Cássia Ferreira de
Published: January 2013

Objectives

To compare the immunohistochemistry (IHC) expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinomas (OSCC) with the gene amplification evaluated by fluorescence in situ hybridization (FISH) and chromogenic in situ hybridization (CISH) and their association with clinicopathological parameters. Additionally, we tested the sensibility and specificity of CISH in comparison with FISH.

Design

Case series study

Setting

Oral surgery and pathology department in a school of dentistry.

Participants

52 patients with histopathological diagnosis of OSCC.

Methods

Tumour tissue samples from 52 patients with OSCC were evaluated by IHC, FISH and CISH using tissue microarray technology. Clinicopathological data from all patients were collected.

Results

EGFR+ rates were 53.8% (28/52) by IHC, 5.8% (3/52) by CISH and 15.4% (8/52) by FISH. Amplification detected by CISH and FISH with IHC negative occurred in 3.8% (2/52), and one case (1.9%) showed amplification detected by CISH and FISH and protein overexpression concomitantly. There were 9.6% FISH+ cases with IHC and CISH negative rates and 6/8 (75%) FISH+ and also EGFR+ cases; however, an association between protein expression and gene amplification was not found for both techniques. IHC and FISH rates were not associated with clinicopathological features. CISH+ rates were associated with T3–T4 status. Compared with FISH assay, CISH reached a sensitivity of 37.5% and specificity of 100%.

Conclusions

There is no association between EGFR expression and gene amplification in OSCC when the IHC is driven to external epitopes of the protein. Although CISH demonstrates specificity, technical problems may influence sensibility when compared with FISH.
Mechanical leaf damage causes localized, but not systemic, changes in leaf movement behavior of the Sensitive Plant, Mimosa pudica (Fabaceae) L.
Authors: Cahill James F. , Bao Tan , Maloney Megan , Kolenosky Carina
Published: January 2013

A small number of species, including Mimosa pudica, use rapid leaf movement as a presumptive defensive strategy. How movement-based defenses change in response to mechanical damage and whether changes are localized or systemic is unknown. This is in contrast to a substantial literature describing how mechanical leaf damage can cause morphological and chemical responses within a diversity of plant species. Depending on the species and the stimuli, these chemical and morphological responses can be localized to the tissues damaged or systemic throughout the plant body. Here we report the results of a small experiment designed to test the following: (i) whether mechanical leaf damage influences subsequent leaf closure behavior, and (ii) whether changes were systemic or localized. To do this, we scored leaves using a behavioral assay (time-to-reopen leaves following a subsequent touch stimuli) for several days before and following mechanical damage. Leaves above and below the damaged leaf were observed, on damaged and undamaged plants, allowing us to assess whether any change was systemic. We found leaf damage caused strong localized effects, greatly increasing the time-to-reopen of the damaged, but not adjacent, leaves. Neither the physiological cause nor fitness consequences of this behavioral shift are known. Interestingly, this altered behavior resulted in damaged leaves remaining “hidden” longer than undamaged leaves. If leaf closure reduces risk of herbivory, there could be adaptive value, analogous to inducible chemical and morphological defenses.
F(G) gravity models based on the ordinary and entropy-corrected holographic dark energy models
Authors: Setare M.R. , Malakolkalami B. , Mohammadipour N.
Published: January 2013

The ordinary and entropy-corrected versions of the holographic dark energy models in the spatially flat Friedmann–Robertson–Walker universe are considered. Then the F(G) modified gravity models as a candidates of dark energy are reconstructed according to the ordinary and entropy-corrected versions of the holographic dark energy models. The EoS parameters corresponding to the F(G) gravity models are obtained. The validity phantom or quintessence models in this framework of the modified gravity are investigated.
Redox-inflammatory synergy in the metabolic syndrome
Authors: Bryan Sean , Baregzay Boran , Spicer Drew , Singal Pawan K. , Khaper Neelam
Published: January 2013

Metabolic syndrome (MetS) comprises interrelated disease states including obesity, insulin resistance and type 2 diabetes (T2DM), dyslipidemia, and hypertension. Essential to normal physiological function, and yet massively damaging in excess, oxidative stress and inflammation are pivotal common threads among the pathologies of MetS. Increasing evidence indicates that redox and inflammatory dysregulation parallels the syndrome's physiological, biochemical, and anthropometric features, leading many to consider the pro-oxidative, pro-inflammatory milieu an unofficial criterion in itself. Left unchecked, cross-promotion of oxidative stress and inflammation creates a feed-forward cycle that can initiate and advance disease progression. Such redox-inflammatory integration is evident in the pathogenesis of obesity, insulin resistance and T2DM, atherogenic dyslipidemia, and hypertension, and is thus hypothesized to be the “common soil” from which they develop. The present review highlights the synergistic contributions of redox-inflammatory processes to each of the components of the MetS.
Design of Liveness-Enforcing Supervisors for S3PR Based on Complementary Places
Authors: Wang Shouguang , Wang Chengying , Yu Yanping
Published: January 2013

In this article, an algorithm is proposed to design liveness-enforcing supervisors for systems of simple sequential processes with resources (S
3
PR) based on complementary places. Firstly, a mixed integer programming (MIP) based deadlock detection method is used to find unmarked strict minimal siphons from an infinite-capacity net. Next, the finite-capacity net, in which liveness can be enforced, is obtained by adding capacity function to the infinite-capacity net. Finally, complementary-place transformation is used to transform the finite-capacity net into an infinite-capacity net. This article focuses on adding a complementary place to each operation place that is related to unmarked siphons, deals with the deadlock problem from a new view point, and hence advances the deadlock control theory. Compared with the existing methods, the new policy is easier to implement for real industrial systems. More importantly, design of a complementary-place supervisor is very easy. Finally, in some cases, the new policy can obtain a structurally simpler supervisor with more permissive behavior than the existing methods do. A flexible manufacturing systems (FMS) example is used to compare the proposed policy with some other methods.
Computation of Minimal Siphons in Petri Nets by Using Binary Decision Diagrams
Authors: Chen Yufeng , Liu Gaiyun
Published: January 2013

Siphons play an important role in the development of deadlock control methods by using Petri nets. The number of siphons increases exponentially with respect to the size of a Petri net. This article presents a symbolic approach to the computation of minimal siphons in Petri nets by using binary decision diagrams (BDD). The siphons of a Petri net can be found via a set of logic conditions. The logic conditions are symbolically modeled by using Boolean algebras. The operations of Boolean algebras are implemented by BDD that are capable of representing large sets of siphons with small shared data structures. The proposed method first uses BDD to compute all siphons of a Petri net and then a binary relation is designed to extract all minimal siphons. Finally, by using a number of examples, the efficiency of the proposed method is verified through different-sized problems.
Modeling and Analysis of TinyOS Sensor Node Firmware
Authors: McInnes Allan I.
Published: January 2013

Wireless sensor networks are an increasingly popular application area for embedded systems. Individual sensor nodes within a network are typically resource-constrained, event-driven, and require a high degree of concurrency. This combination of requirements motivated the development of the widely used TinyOS sensor node operating system. The TinyOS concurrency model is a lightweight nonpreemptive system designed to suit the needs of typical sensor network applications. Although the TinyOS concurrency model is easier to reason about than preemptive threads, it can still give rise to undesirable behavior due to unexpected interleavings of related tasks, or unanticipated preemption by interrupt handlers. To aid TinyOS developers in understanding the behavior of their programs we have developed a technique for using the process algebra Communicating Sequential Processes (CSP) to model the interactions between TinyOS components, and between an application and the TinyOS scheduling and preemption mechanisms. Analysis of the resulting models can help TinyOS developers to discover and diagnose concurrency-related errors in their designs that might otherwise go undetected until after the application has been widely deployed. Such analysis is particularly valuable for the TinyOS components that are used as building blocks for a large number of other applications, since a subtle or sporadic error in a widely deployed building block component could be extremely costly to repair.
Formal Validation of a Deterministic MAC Protocol
Authors: Godary-Dejean Karen , Andreu David
Published: January 2013

This article deals with the formal validation of STIMAP, a medium access protocol that has been designed to meet the specific requirements of an implantable network-based neuroprosthesis. This article presents the modeling and the validation of its medium access, using model checking on Time Petri Nets. Doing so, we show that existent formal methods and tools are not perfectly suitable for the validation of real systems, especially when some hardware parameters have to be considered. This article then presents how these difficulties have been managed during the modeling and verification phases, and gives the validation results for STIMAP, providing constraints to respect.
Formal Verification of Downtimeless System Evolution in Embedded Automation Controllers
Authors: Sünder Christoph , Vyatkin Valeriy , Zoitl Alois
Published: January 2013

This article presents a new formal approach to validation of on-the-fly modification of control software in automation systems. The concept of downtimeless system evolution (DSE) is introduced. The DSE is essentially based on the use of IEC 61499 system architecture and formal modeling and verification of the hardware and software of an automation device. The validation is performed by means of two complimentary techniques: analytic calculations and formal verification by model-checking.
Contextual and active learning-based affect-sensing from virtual drama improvisation
Authors: Zhang Li
Published: January 2013

Affect interpretation from open-ended drama improvisation is a challenging task. This article describes experiments in using latent semantic analysis to identify discussion themes and potential target audiences for those improvisational inputs without strong affect indicators. A context-based affect-detection is also implemented using a supervised neural network with the consideration of emotional contexts of most intended audiences, sentence types, and interpersonal relationships. In order to go beyond the constraints of predefined scenarios and improve the system's robustness, min-margin-based active learning is implemented. This active learning algorithm also shows great potential in dealing with imbalanced affect classifications. Evaluation results indicated that the context-based affect detection achieved an averaged precision of 0.826 and an averaged recall of 0.813 for affect detection of the test inputs from the Crohn's disease scenario using three emotion labels: positive, negative, and neutral, and an averaged precision of 0.868 and an average recall of 0.876 for the test inputs from the school bullying scenario. Moreover, experimental evaluation on a benchmark data set for active learning demonstrated that active learning was able to greatly reduce human annotation efforts for the training of affect detection, and also showed promising robustness in dealing with open-ended example inputs beyond the improvisation of the chosen scenarios.
Revving the rover
Authors: Wright Alex
Published: January 2013

The new Mars rover has attracted plenty of attention for its planetary gymnastics, but the big breakthroughs are under the hood.
A new model for healthcare
Authors: Greengard Samuel
Published: January 2013

Computer modeling is radically redefining healthcare and epidemiology by providing new tools for understanding the impact of different intervention strategies.
The tangled web we have woven
Authors: Moglen Eben
Published: January 2013

Seeking to protect the fundamental privacy of network interactions.
Cloud services certification
Authors: Sunyaev Ali , Schneider Stephan
Published: January 2013

How to address the lack of transparency, trust, and acceptance in cloud services.
Thinking methodically about performance
Authors: Gregg Brendan
Published: January 2013

The USE method addresses shortcomings in other commonly used methodologies.
Symbolic execution for software testing
Authors: Cadar Cristian , Sen Koushik
Published: January 2013

The challenges---and great promise---of modern symbolic execution techniques, and the tools to help implement them.
Power challenges may end the multicore era
Authors: Esmaeilzadeh Hadi , Blem Emily , Amant Renée St. , Sankaralingam Karthikeyan , Burger Doug
Published: January 2013

Starting in 2004, the microprocessor industry has shifted to multicore scaling---increasing the number of cores per die each generation---as its principal strategy for continuing performance growth. Many in the research community believe that this exponential core scaling will continue into the hundreds or thousands of cores per chip, auguring a parallelism revolution in hardware or software. However, while transistor count increases continue at traditional Moore's Law rates, the per-transistor speed and energy efficiency improvements have slowed dramatically. Under these conditions, more cores are only possible if the cores are slower, simpler, or less utilized with each additional technology generation. This paper brings together transistor technology, processor core, and application models to understand whether multicore scaling can sustain the historical exponential performance growth in this energy-limited era. As the number of cores increases, power constraints may prevent powering of all cores at their full speed, requiring a fraction of the cores to be powered off at all times. According to our models, the fraction of these chips that is "dark" may be as much as 50% within three process generations. The low utility of this "dark silicon" may prevent both scaling to higher core counts and ultimately the economic viability of continued silicon scaling. Our results show that core count scaling provides much less performance gain than conventional wisdom suggests. Under (highly) optimistic scaling assumptions---
for parallel workloads
---multicore scaling provides a 7.9× (23% per year) over ten years. Under more conservative (realistic) assumptions, multicore scaling provides a total performance gain of 3.7× (14% per year) over ten years, and obviously less when sufficiently parallel workloads are unavailable. Without a breakthrough in process technology or microarchitecture, other directions are needed to continue the historical rate of performance improvement.