bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycine receptor antibody-associated epilepsy in a boy aged 4 years
Authors: Ude Chinwe , Ambegaonkar Gautam
Published: October 2016

Our patient was a previously normal boy who presented to his local hospital with an explosive onset of prolonged seizures and encephalopathy. He was treated for a presumed central nervous system infection and initial neuroimaging was normal. Despite treatment with antibiotics and antiepileptic drugs (AEDs), he remained encephalopathic and became ataxic over the next 48 hours, not related to medication. The seizures also proved resistant to treatment despite polytherapy with AEDs, and he required immune-modulatory treatment, intravenous methylprednisolone and intravenous immunoglobulin, in addition to the AEDs to achieve seizure control. The ataxia also improved following treatment. The initial EEG was normal but subsequent EEGs, separated by a week each, were abnormal and revealed subtle atypical ‘delta-brush-like waves’. The patient's serum and cerebrospinal fluid were tested for autoantibodies, and he was found to be positive for glycine receptor antibodies that are neuronal antibodies.
Unusual case of pheochromocytoma presenting with diabetic ketoacidosis
Authors: Sedhai Yub Raj , Reddy Kruthika , Patel Dhruvan , Lozada James A
Published: October 2016

Pheochromocytoma is a rare catecholamine-secreting tumour that arises from chromaffin cells in the adrenal medulla or extra-adrenal sympathetic ganglia. It classically presents with paroxysmal headaches, hypertension, palpitations and sweating related to catecholamine excess. Diabetes is reported to be present in approximately one-third of patients with pheochromocytoma; however, diabetic ketoacidosis is an extremely rare complication. We present a case of an African-American male aged 30 years who initially presented with diabetic ketoacidosis and hypertensive urgency whose blood pressure and glycaemic control improved remarkably following tumour excision. We will discuss this unusual presentation of pheochromocytoma along with a management approach for such adrenal incidentalomas.
Everolimus-associated stomatitis in a patient who had renal transplant
Authors: Ji Yisi D , Aboalela Ali , Villa Alessandro
Published: October 2016

Everolimus is used as an immunosuppressant in renal allograft transplant rejection and in metastatic breast cancer treatment. One side effect of everolimus is stomatitis, referred to as mammalian target of rapamycin inhibitor-associated stomatitis. This side effect can affect treatment course and contribute to discontinuation of therapy or dose reduction, previously reported in the treatment of metastatic breast cancer. Here, we present a case of everolimus-associated stomatitis with a novel management method with intralesional triamcinolone that allows for continuous course of everolimus.
Risk factors for bleb-related infection following trabeculectomy surgery: ocular surface findings—a case–control study
Authors: Rai Poornima A , Barton Keith , Murdoch Ian E
Published: October 2016

Purpose

Bleb-related infection (BRI) is a devastating complication of trabeculectomy surgery. The aim of this study was to identify ocular risk factors for BRI with specific emphasis on ocular surface parameters. It has been suggested that the frequency has increased since the introduction of antimetabolites, particularly mitomycin C.

Design

A case–control study.

Method

A clinical study of BRI following trabeculectomy surgery to investigate risk factors by documenting historical data review from patients records, self-reported questionnaire specific to ocular surface symptoms and a repeat detailed clinical examination of the lid, ocular surface and tear film.

Results

Twenty-eight cases and 31 controls were assessed. The overwhelming risk factor for development of BRI was chronic blepharitis (multivariate analysis OR 16.3 (1.687 to 157.44) p=0.016). No increased risk was identified with the antimetabolite used during trabeculectomy surgery (p=0.38) or the type of conjunctival reflection adopted for surgery (p=0.38). Neither age (p=0.32) nor dry eyes (p=0.13) were identified as risk factors.

Conclusion

An increased risk of BRI was identified in eyes with chronic blepharitis. To minimise the risk of infection following trabeculectomy surgery, it may be advisable to manage the lid disease in these patients prior to performing trabeculectomy surgery or offer an alternative treatment such as a shunt.

Trial registration number

RAIQ1001.
Dietary fat guidelines have no evidence base: where next for public health nutritional advice?
Authors: Harcombe Zoë
Published: October 2016

Introduction

National dietary guidelines were introduced in 1977 and 1983, by the US and UK governments, with the aim of reducing coronary heart disease (CHD) mortality. The 2 specific dietary fat recommendations were to reduce total fat and saturated fat consumption to 30% and 10% of total energy intake, respectively.

Methods

4 systematic reviews (3 with meta-analysis) were undertaken to examine the evidence for these dietary fat guidelines: (1) randomised controlled trial (RCT) and (2) prospective cohort (PC) evidence at the time the guidelines were introduced; and (3) RCT and (4) PC evidence currently available. This narrative review examines all evidence collated.

Results

The RCT and PC evidence available to the dietary committees did not support the introduction of the dietary fat guidelines. The RCT and PC evidence currently available does not support the extant recommendations. Furthermore, the quality of the evidence is so poor that it could not be relied on had it provided support.

Conclusions

Dietary fat guidelines have prevailed for almost 40 years. The evidence base at the time of their introduction has been examined for the first time and found lacking. Evidence currently available provides no additional support. Public health opinion differed when the guidelines were introduced. Opposition to the guidelines is becoming more strident. Substantial increases in diet-related illness over the past four decades, particularly obesity and type 2 diabetes, indicate that a review of dietary advice is warranted.
OPTIMUM: a protocol for a multicentre randomised controlled trial comparing Out Patient Talc slurry via Indwelling pleural catheter for Malignant pleural effusion vs Usual inpatient Management
Authors: Sivakumar P , Douiri A , West A , Rao D , Warwick G , Chen T , Ahmed L
Published: October 2016

Introduction

The development of malignant pleural effusion (MPE) results in disabling breathlessness, pain and reduced physical capability with treatment a palliative strategy. Ambulatory management of MPE has the potential to improve quality of life (QoL). The OPTIMUM trial is designed to determine whether full outpatient management of MPE with an indwelling pleural catheter (IPC) and pleurodesis improves QoL compared with traditional inpatient care with a chest drain and talc pleurodesis. OPTIMUM is currently open for any centres interested in collaborating in this study.

Methods and analysis

OPTIMUM is a multicentre non-blinded randomised controlled trial. Patients with a diagnosis of MPE will be identified and screened for eligibility. Consenting participants will be randomised 1:1 either to an outpatient ambulatory pathway using IPCs and talc pleurodesis or standard inpatient treatment with chest drain and talc pleurodesis as per British Thoracic Society guidelines. The primary outcome measure is global health-related QoL at 30 days measured using the EORTC QLQ-C30 questionnaire. Secondary outcome measures include breathlessness and pain measured using a 100 mm Visual Analogue Scale and health-related QoL at 60 and 90 days. A sample size of 142 patients is needed to demonstrate a clinically significant difference of 8 points in global health status at 30 days, for an 80% power and a 5% significance level.

Ethics and dissemination

The study has been approved by the NRES Committee South East Coast—Brighton and Sussex (reference 15/LO/1018). The trial results will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration numbers

UKCRN19615 andISRCTN15503522; Pre-results.
Symmetrized exponential oscillator
Authors: Znojil Miloslav
Published: October 2016

Several properties of bound states in potential V(x) = g2 exp[Formula: see text]x[Formula: see text] are studied. Firstly, with the emphasis on the reliability of our arbitrary-precision construction, wave functions are considered in the two alternative (viz. asymptotically decreasing or regular) exact Bessel-function forms which obey the asymptotic or matching conditions, respectively. The merits of the resulting complementary transcendental secular equation approaches are compared and their applicability is discussed.
Neutrino oscillation, finite self-mass and general Yang–Mills symmetry
Authors: Hsu Jong-Ping
Published: October 2016

The conservation of lepton number is assumed to be associated with a general Yang–Mills (gYM) symmetry. New transformations involve (Lorentz) vector gauge functions and characteristic phase functions, and they form a group. General Yang–Mills fields are associated with new fourth-order equations and linear potentials. Lepton self-masses turn out to be finite and proportional to the inverse of lepton masses, which implies that neutrinos should have nonzero masses. Thus, gYM symmetry could provide an understanding of neutrino oscillations and suggests that neutrinos with masses and very weak leptonic force may play a role in dark matter.
Hadron diffractive production at ultrahigh energies and shadow effects
Authors: Anisovich V. V. , Matveev M. A. , Nikonov V. A.
Published: October 2016

Shadow effects at collisions of hadrons with light nuclei at high energies were subject of scientific interest of V.N. Gribov, first, we mean his study of the hadron-deuteron scattering, see Sov. Phys. JETP 29, 483 (1969) [Zh. Eksp. Teor. Fiz. 56, 892 (1969)] and discovery of the reinforcement of shadowing due to inelastic diffractive rescatterings. It turns out that the similar effect exists on hadron level though at ultrahigh energies.

Diffractive production is considered in the ultrahigh energy region where pomeron exchange amplitudes are transformed into black disk ones due to rescattering corrections. The corresponding corrections in hadron reactions [Formula: see text] with small momenta transferred ([Formula: see text], [Formula: see text]) are calculated in terms of the [Formula: see text]-matrix technique modified for ultrahigh energies. Small values of the momenta transferred are crucial for introducing equations for amplitudes. The three-body equation for hadron diffractive production reaction [Formula: see text] is written and solved precisely in the eikonal approach. In the black disk regime final state scattering processes do not change the shapes of amplitudes principally but dump amplitudes by a factor [Formula: see text]; initial state rescatterings result in additional factor [Formula: see text]. In the resonant disk regime initial and final state scatterings damp strongly the production amplitude that corresponds to [Formula: see text] at [Formula: see text] in this mode.
Early formed astrophysical objects and cosmological antimatter
Authors: Dolgov Alexander D.
Published: October 2016

Astronomical observations of recent years show that the universe at high redshifts (about ten) is densely populated by early formed objects: bright galaxies, quasars, gamma-bursters, and it contains a lot of metals and dust. Such a rich variety of early formed objects have not been expected in the standard model of formation of astrophysical objects. There is serious tension between the standard theory and the observations. We describe the model which relaxes this tension and nicely fits the data. The model naturally leads to the creation of cosmologically significant antimatter which may be abundant even in the Galaxy. Phenomenological consequences of our scenario and the possibility of distant registration of antimatter are discussed.
Electromagnetic production of positrons and electrons in collisions of heavy nuclei
Authors: Khriplovich I. B.
Published: October 2016

We consider the electromagnetic production of positrons and electrons in collisions of slow heavy nuclei. This process is dominated by emission of positrons, with the electrons captured by nucleus.
Beta functions in Chirally deformed supersymmetric sigma models in two dimensions
Authors: Vainshtein Arkady
Published: October 2016

We study two-dimensional sigma models where the chiral deformation diminished the original [Formula: see text] supersymmetry to the chiral one, [Formula: see text]. Such heterotic models were discovered previously on the world sheet of non-Abelian stringy solitons supported by certain four-dimensional [Formula: see text] theories. We study geometric aspects and holomorphic properties of these models, and derive a number of exact expressions for the [Formula: see text] functions in terms of the anomalous dimensions analogous to the NSVZ [Formula: see text] function in four-dimensional Yang-Mills. Instanton calculus provides a straightforward method for the derivation.
Electronic and optical properties of AlN under pressure: DFT calculations
Authors: Javaheri Sahar , Boochani Arash , Babaeipour Manuchehr , Naderi Sirvan
Published: October 2016

Structural, elastic, optical, and electronic properties of wurtzite (WZ), zinc-blende (ZB), and rocksalt (RS) structures of AlN are investigated using the first-principles method and within the framework of density functional theory (DFT). Lattice parameters, bulk modulus, shear modulus, Young’s modulus, and elastic constants are calculated at zero pressure and compared with other experimental and theoretical results. The wurtzite and zinc-blende structures have a transition to rocksalt phase at the pressures of 12.7 GPa and 14 GPa, respectively. The electronic properties are calculated using both GGA and EV-GGA approximations; the obtained results by EV-GGA approximation are in much better agreement with the available experimental data. The RS phase has the largest bandgap with an amount of 4.98 eV; by increasing pressure, this amount is also increased. The optical properties like dielectric function, energy loss function, refractive index, and extinction coefficient are calculated under pressure using GGA approximation. Inter-band transitions are investigated using the peaks of imaginary part of the dielectric function and these transitions mainly occur from N-2[Formula: see text] to Al-3[Formula: see text] levels. The results show that the RS structure has more different properties than the WZ and ZB structures.
EFFECT OF BORATES AND SILICATES ON WEARING PROPERTIES OF MAO COATINGS
Authors: ZHANG Yu , ZHAO YAN-WEI , XIANG NAN , SONG REN-GUO
Published: October 2016

In the present study, microarc oxidation (MAO) coatings were formed on ZL101A aluminum alloy in an electrolytic bath containing 3[Formula: see text]g/L KOH [Formula: see text] 2[Formula: see text]g/L Na2WO[Formula: see text] 4[Formula: see text]g/L KF. The morphology and wearing behavior were investigated. In both electrolytes, the additives were borates (Na2B4O718[Formula: see text]g/L) and silicates (Na2SiO3 18[Formula: see text]g/L), respectively. It was found that the coating formed in borates-containing electrolyte was of compact and smooth structure than that of the one formed in silicates-containing electrolyte at the optimum treatment time. It was found that all the coatings were composed of á-Al2O3 and ã-Al2O3. The microhardness and wear tests proved that the coating formed in borates-containing electrolyte was having better mechanical properties than those of the coating formed in silicates-containing electrolyte.
MICROWAVE SYNTHESIS AND CHARACTERIZATION OF WASTE SOYBEAN OIL-BASED GEMINI IMIDAZOLINIUM SURFACTANTS WITH CARBONATE LINKAGE
Authors: TRIPATHY DIVYA BAJPAI , MISHRA ANURADHA
Published: October 2016

Gemini surfactants are presently gaining attention due to their unusual self-assembling characteristics and incomparable interfacial activity. Current research work involves the cost-effective microwave (MW) synthesis of waste soybean oil-based gemini imidazolinium surfactants (GIS) having a carbonate linkage in its spacer moiety. Structural characterizations of the materials have been done using FT-IR, 1H-NMR and [Formula: see text]C-NMR. Using indigenous and natural material as base and MW as energy source for synthesizing the GIS with easily degradable chemical moiety make them to be labeled as green surfactants.
Solvability of coupled FBSDEs with diagonally quadratic generators
Authors: Luo Peng , Tangpi Ludovic
Published: October 2016

We study the well-posedness for multi-dimensional and coupled systems of forward–backward SDEs when the generator can be separated into a quadratic and a subquadratic part. We obtain the existence and uniqueness of the solution on a small time interval. Moreover, the continuity and differentiability with respect to the initial value are presented.
Non-equispaced B-spline wavelets
Authors: Jansen Maarten
Published: October 2016

This paper has three main contributions. The first is the construction of wavelet transforms from B-spline scaling functions defined on a grid of non-equispaced knots. The new construction extends the equispaced, biorthogonal, compactly supported Cohen–Daubechies–Feauveau wavelets. The new construction is based on the factorization of wavelet transforms into lifting steps. The second and third contributions are new insights on how to use these and other wavelets in statistical applications. The second contribution is related to the bias of a wavelet representation. It is investigated how the fine scaling coefficients should be derived from the observations. In the context of equispaced data, it is common practice to simply take the observations as fine scale coefficients. It is argued in this paper that this is not acceptable for non-interpolating wavelets on non-equidistant data. Finally, the third contribution is the study of the variance in a non-orthogonal wavelet transform in a new framework, replacing the numerical condition as a measure for non-orthogonality. By controlling the variances of the reconstruction from the wavelet coefficients, the new framework allows us to design wavelet transforms on irregular point sets with a focus on their use for smoothing or other applications in statistics.
d-Refinable (dual) pseudo-splines and their regularities
Authors: Shen Yanfeng , Yang Shouzhi , Yuan Dehui
Published: October 2016

In this paper, we introduce the concept of [Formula: see text]-dilation (dual) pseudo-splines in [Formula: see text] with dilation [Formula: see text], characterize the linear independence of the integer shifts, the subdivision schemes of polynomial reproduction and Hölder regularity for (dual) pseudo-splines with general dilation. We present a new method to determine the Hölder regularity of refinable functions with general dilation [Formula: see text]. Furthermore, we compare the regularities between pseudo-splines and dual ones.
Electroconductive films based on amino-substituted tetraphenylporphyrins and their metal copper complexes
Authors: Tesakova Mariya V. , Semeikin Aleksandr S. , Parfenyuk Vladimir I.
Published: October 2016

Amino-substituted tetraphenylporphyrins (5,10,15,20-tetrakis(4′-aminophenyl)porphyrin, 5-(4′-aminophenyl)–10,15,20-triphenylporphyrin) and their copper complexes in dichloromethane and ethanol were electropolymerized by the cyclic voltammetry method and their electrochemical properties were studied. The polyporphyrin films obtained by electro-oxidation transmit electricity and possess semiconductor properties of different types. The poly-5,10,15,20-tetrakis(4′-aminophenyl)porphyrin films obtained from different solvents are similar to each other in chemical composition but different in morphology. The polyporphyrin film surface morphology was studied by AFM microscopy.
Approximations to defect chemistry in Bi4Ti3O12
Authors: Martínez-Morales Ma. del Carmen , Romero-Serrano José Antonio , Gómez-Yáñez Carlos , Rojas Luis Lartundo
Published: October 2016

Bismuth titanate (Bi4Ti3O[Formula: see text] or BiTO) is known for its high resistance to dielectric fatigue and relatively large remnant polarization. Owing to these characteristics, it has been applied in FeRAM memory. BiTO is also known to be a potential ionic conductor. In both applications, crystalline defects play an important role. In this work, a standard thermochemical equilibrium procedure is used to analyze defect chemistry in BiTO. The results indicate a strong oxidized state. To obtain a reduced condition, extremely low oxygen partial pressures and high temperatures have to be achieved. Even at normal conditions, results show a relatively high concentration of holes, which is in agreement with the [Formula: see text]-type leaking experimentally observed, relatively high concentration of oxygen vacancies, which suggest the potential application of BiTO as ion conductor, and relative high concentration of bismuth vacancies, in accordance with the known problem of bismuth volatilization observed during the processing of this material.
The total number of acini remains constant throughout postnatal rat lung development
Authors: Barré Sébastien F. , Haberthür David , Cremona Tiziana P. , Stampanoni Marco , Schittny Johannes C.
Published: October 2016

The pulmonary airways are subdivided into conducting and gas-exchanging airways. The small tree of gas-exchanging airways which is fed by the most distal conducting airway represents an acinus. Very little is known about the development of the number of acini. The goal of this study was to estimate their number throughout rat postnatal development. Right middle rat lung lobes were obtained at postnatal day 4–60, stained with heavy metals, paraffin embedded, and scanned by synchrotron radiation-based X-ray tomographic microscopy or imaged with micro computed tomography after critical point drying. The acini were counted by detection of the transitional bronchioles [bronchioalveolar duct junction (BADJ)] by using morphological criteria (thickness of the walls of airways and appearance of alveoli) during examination of the resulting three-dimensional (3D) image stacks. Between postnatal days 4–60, the number of acini per lung remained constant (5,840 ± 547 acini), but their volume increased significantly. We concluded that the acini are formed before the end of the saccular stage (before postnatal day 4) and that the developmental increase of the lung volume is achieved by an increase of the acinar volume and not by an increase of their number. Furthermore, our results propose that the bronchioalveolar stem cells, which are residing in the BADJ, are as constant in their location as the BADJ itself.
Maternal vascular responses to hypoxia in a rat model of intrauterine growth restriction
Authors: Aljunaidy Mais M. , Morton Jude S. , Cooke Christy-Lynn , Davidge Sandra T.
Published: October 2016

Intrauterine growth restriction (IUGR) is a common pregnancy complication and is a leading cause of fetal morbidity and mortality. Placental hypoxia contributes to adverse fetal consequences, such as IUGR. Exposing pregnant rats to hypoxia can lead to IUGR; however, assessment of maternal vascular function in a rat model of hypoxia, and the mechanisms that may contribute to adverse pregnancy outcomes, has not been extensively studied. We hypothesized that exposing pregnant rats to hypoxia will affect maternal systemic vascular function and increase the uterine artery resistance index (RI), which will be associated with IUGR. To test this hypothesis, pregnant rats were kept in normoxia (21% O2) or hypoxia (11% O2) from gestational day (GD) 6 to 20. Maternal blood pressure, uteroplacental resistance index (RI) (ultrasound biomicroscopy), and vascular function (wire myography) were assessed in uterine and mesenteric arteries. Fetal weight was significantly reduced ( P < 0.001), while maternal blood pressure was increased ( P < 0.05) in rats exposed to hypoxia. Maternal vascular function was also affected after exposure to hypoxia, including impaired endothelium-dependent vasodilation responses to methacholine in isolated uterine arteries (pEC50 normoxia: 6.55 ± 0.23 vs. hypoxia: 5.02 ± 0.35, P < 0.01) and a reduced uterine artery RI in vivo (normoxia: 0.63 ± 0.04 vs. hypoxia: 0.53 ± 0.01, P < 0.05); associated with an increase in umbilical vein RI (normoxia: 0.35 ± 0.02 vs. hypoxia: 0.45 ± 0.04, P < 0.05). These data demonstrate maternal and fetal alterations in vascular function due to prenatal exposure to hypoxia. Further, although there was a compensatory reduction in uterine artery RI in the hypoxia groups, this was not sufficient to prevent IUGR.
ILK and cytoskeletal architecture: an important determinant of AQP2 recycling and subsequent entry into the exocytotic pathway
Authors: Mamuya Fahmy A. , Cano-Peñalver Jose Luis , Li Wei , Rodriguez Puyol Diego , Rodriguez Puyol Manuel , Brown Dennis , de Frutos Sergio , Lu Hua Ann Jenny
Published: October 2016

Within the past decade tremendous efforts have been made to understand the mechanism behind aquaporin-2 (AQP2) water channel trafficking and recycling, to open a path toward effective diabetes insipidus therapeutics. A recent study has shown that integrin-linked kinase (ILK) conditional-knockdown mice developed polyuria along with decreased AQP2 expression. To understand whether ILK also regulates AQP2 trafficking in kidney tubular cells, we performed in vitro analysis using LLCPK1 cells stably expressing rat AQP2 (LLC-AQP2 cells). Upon treatment of LLC-AQP2 cells with ILK inhibitor cpd22 and ILK-siRNA, we observed increased accumulation of AQP2 in the perinuclear region, without any significant increase in the rate of endocytosis. This perinuclear accumulation did not occur in cells expressing a serine-256-aspartic acid mutation that retains AQP2 in the plasma membrane. We then examined clathrin-mediated endocytosis after ILK inhibition using rhodamine-conjugated transferrin. Despite no differences in overall transferrin endocytosis, the endocytosed transferrin also accumulated in the perinuclear region where it colocalized with AQP2. These accumulated vesicles also contained the recycling endosome marker Rab11. In parallel, the usual vasopressin-induced AQP2 membrane accumulation was prevented after ILK inhibition; however, ILK inhibition did not measurably affect AQP2 phosphorylation at serine-256 or its dephosphorylation at serine-261. Instead, we found that inhibition of ILK increased F-actin polymerization. When F-actin was depolymerized with latrunculin, the perinuclear located AQP2 dispersed. We conclude that ILK is important in orchestrating dynamic cytoskeletal architecture during recycling of AQP2, which is necessary for its subsequent entry into the exocytotic pathway.
Foot placement relies on state estimation during visually guided walking
Authors: Maeda Rodrigo S. , O'Connor Shawn M. , Donelan J. Maxwell , Marigold Daniel S.
Published: October 2016

As we walk, we must accurately place our feet to stabilize our motion and to navigate our environment. We must also achieve this accuracy despite imperfect sensory feedback and unexpected disturbances. In this study we tested whether the nervous system uses state estimation to beneficially combine sensory feedback with forward model predictions to compensate for these challenges. Specifically, subjects wore prism lenses during a visually guided walking task, and we used trial-by-trial variation in prism lenses to add uncertainty to visual feedback and induce a reweighting of this input. To expose altered weighting, we added a consistent prism shift that required subjects to adapt their estimate of the visuomotor mapping relationship between a perceived target location and the motor command necessary to step to that position. With added prism noise, subjects responded to the consistent prism shift with smaller initial foot placement error but took longer to adapt, compatible with our mathematical model of the walking task that leverages state estimation to compensate for noise. Much like when we perform voluntary and discrete movements with our arms, it appears our nervous systems uses state estimation during walking to accurately reach our foot to the ground.

NEW & NOTEWORTHY Accurate foot placement is essential for safe walking. We used computational models and human walking experiments to test how our nervous system achieves this accuracy. We find that our control of foot placement beneficially combines sensory feedback with internal forward model predictions to accurately estimate the body's state. Our results match recent computational neuroscience findings for reaching movements, suggesting that state estimation is a general mechanism of human motor control.
Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4+ T Cells
Authors: Huang Peng , Zhou Yuxiang , Liu Zan , Zhang Pihong
Published: October 2016

Decreased Th1/Th2 ratio is one of the major characteristics of immunosuppression in sepsis. Both membrane adhesive protein Annexin-A1 (ANXA1) and transcription factor GATA-3 have been reported to play important roles in T cell differentiation. However, the relationship between ANXA1 and GATA-3 in Th1/Th2 shift is unknown. Our study investigated the interaction effects of ANXA1 and GATA-3 to influence T cell differentiation in CD4+ T cells. We found that GATA-3 and ANXA1 were coexpressed on Th0/Th1/Th2 cytoplasm and nuclear. Overexpressed ANXA1 significantly increased the expression of IFNγ and reduced IL-4 expression in T cells, while ANXA1-silenced T cells exhibited decreased production of IFNγ and increased production of IL-4. Knockdown of ANXA1 promoted higher expression level of GATA-3 and low level of T-box transcription factor (T-bet/Tbx21). Further study demonstrated that ANXA1 regulated GATA-3 expression through the formyl peptide receptor like-1 (FPRL-1) downstream signaling pathways ERK and PKB/Akt. These results suggested that ANXA1 modulates GATA-3/T-bet expression induced Th0/Th1 differentiation. Moreover, we found that GATA-3 inhibited ANXA1 expression by binding to its promoter for the first time. It is proposed that the interactions between ANXA1 and GATA-3 may provide clues to understand the immunosuppression and have potential as new therapeutic targets in immunotherapy after sepsis.
Almost Periodic Dynamics for Memristor-Based Shunting Inhibitory Cellular Neural Networks with Leakage Delays
Authors: Lu Lin , Li Chaoling
Published: October 2016

We investigate a class of memristor-based shunting inhibitory cellular neural networks with leakage delays. By applying a new Lyapunov function method, we prove that the neural network which has a unique almost periodic solution is globally exponentially stable. Moreover, the theoretical findings of this paper on the almost periodic solution are applied to prove the existence and stability of periodic solution for memristor-based shunting inhibitory cellular neural networks with leakage delays and periodic coefficients. An example is given to illustrate the effectiveness of the theoretical results. The results obtained in this paper are completely new and complement the previously known studies of Wu (2011) and Chen and Cao (2002).
Topology Optimization of 3-DOF Peristaltic Structure Robot Based on Vector Continuous Mapping Matrix
Authors: Wang Gao , Zhu Dachang , Liu Ning
Published: October 2016

A mechanism for topology optimization of 3-DOF parallel peristaltic structure robot with vector continuous mapping matrix using Solid Isotropic Material with Penalization (SIMP) method is presented in this paper. We focus on how to prevent the differential motion consistency between parallel prototype mechanisms with peristaltic structure. As the conventional parallel robot joints/hinges are no longer needed after topology optimization, therefore, we renamed this kind of 3-DOF robot structures as peristaltic structure. In the proposed method, the vector continuous mapping matrix is built as stress/strain transfer direction conditions for topology optimization of peristaltic structure, and SIMP method is used for multi-inputs and multioutputs decided by parallel prototype mechanisms. Some numerical examples are presented to illustrate the validity of the proposed method.
An Efficient Deterministic-Stochastic Model of the Human Body Exposed to ELF Electric Field
Authors: Šušnjara Anna , Poljak Dragan
Published: October 2016

The paper deals with the deterministic-stochastic model of the human body represented as cylindrical antenna illuminated by a low frequency electric field. Both analytical and numerical (Galerkin-Bubnov scheme of Boundary Element Method) deterministic solutions of the problem are outlined. This contribution introduces the new perspective of the problem: the variability inherent to input parameters, such as the height of the body, the shape of the body, and the conductivity of body tissue, is propagated to the output of interest (induced axial current). The stochastic approach is based on the stochastic collocation (SC) method. Computational examples show the mean trend of both analytically and numerically computed axial current with the confidence margins for different set of input random variables. The results point out the possibility of improving the efficiency in calculation of basic restriction parameter values in electromagnetic dosimetry.
Steady-State Thermoelastic Analytical Solutions for Insulated Pipelines
Authors: Fraldi M. , Esposito L. , Carannante F. , Cutolo A. , Nunziante L.
Published: October 2016

A steady-state thermoelastic analytical solution for a multilayer hollow cylinder, composed of an arbitrary number of phases and subject to both radial pressure and temperature gradient, is presented. By assuming each phase to be homogeneous and thermally isotropic and by varying the mechanical and thermal constitutive parameters, a sensitivity analysis has been performed with the aim of finally applying the study to the mechanical behaviour of an industrial pipeline composed of three phases (steel, insulating coating, and polyethylene) under the action of the above-mentioned load conditions. By making reference to a classical Hencky-von Mises criterion, the stress profiles along the thickness of the layers have been carried out, also localizing the onset of plasticity as a function of the temperature variations, material properties, and geometrical features characterizing the composite structure of interest. At the end, some numerical results of practical interest in the engineering applications have been specialized to three different insulated coating materials (expanded polyurethane, laminate glass, and syntactic foam), to highlight the cases in which thermal properties and loads can significantly interfere with the mechanical response in pipes, in terms of stresses, in this way suggesting possible strategies for avoiding unexpected failure and supporting the optimal structural design of these systems.
ADMM-EM Method forL1-Norm Regularized Weighted Least Squares PET Reconstruction
Authors: Teng Yueyang , Sun Hang , Guo Chen , Kang Yan
Published: October 2016

TheL1-norm regularization is usually used in positron emission tomography (PET) reconstruction to suppress noise artifacts while preserving edges. The alternating direction method of multipliers (ADMM) is proven to be effective for solving this problem. It sequentially updates the additional variables, image pixels, and Lagrangian multipliers. Difficulties lie in obtaining a nonnegative update of the image. And classic ADMM requires updating the image by greedy iteration to minimize the cost function, which is computationally expensive. In this paper, we consider a specific application of ADMM to theL1-norm regularized weighted least squares PET reconstruction problem. Main contribution is derivation of a new approach to iteratively and monotonically update the image while self-constraining in the nonnegativity region and the absence of a predetermined step size. We give a rigorous convergence proof on the quadratic subproblem of the ADMM algorithm considered in the paper. A simplified version is also developed by replacing the minima of the image-related cost function by one iteration that only decreases it. The experimental results show that the proposed algorithm with greedy iterations provides a faster convergence than other commonly used methods. Furthermore, the simplified version gives a comparable reconstructed result with far lower computational costs.
Effect of Casting Conditions on the Fracture Strength of Al-5 Mg Alloy Castings
Authors: Basuny Fawzia Hamed , Ghazy Mootaz , Kandeil Abdel-Razik Y. , El-Sayed Mahmoud Ahmed
Published: October 2016

During the transient phase of filling a casting running system, surface turbulence can cause the entrainment of oxide films into the bulk liquid. Previous research has suggested that the entrained oxide film would have a deleterious effect on the reproducibility of the mechanical properties of Al cast alloys. In this work, the Weibull moduli for the ultimate tensile strength (UTS) and % elongation of sand cast bars produced under different casting conditions were compared as indicators of casting reliability which was expected to be a function of the oxide film content. The results showed that the use of a thin runner along with the use of filters can significantly eliminate the surface turbulence of the melt during mould filling which would lead to the avoidance of the generation and entrainment of surface oxide films and in turn produce castings with more reliable and reproducible mechanical properties compared to the castings produced using conventional running systems.
Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody
Authors: Segal Neil H. , Logan Theodore F. , Hodi F. Stephen , McDermott David , Melero Ignacio , Hamid Omid , Schmidt Henrik , Robert Caroline , Chiarion-Sileni Vanna , Ascierto Paolo A. , Maio Michele , Urba Walter J. , Gangadhar Tara C. , Suryawanshi Satyendra , Neely Jaclyn , Jure-Kunkel Maria , Krishnan Suba , Kohrt Holbrook , Sznol Mario , Levy Ronald
Published: October 2016

Purpose: Urelumab is an agonist antibody to CD137 with potential application as an immuno-oncology therapeutic. Data were analyzed to assess safety, tolerability, and pharmacodynamic activity of urelumab, including the dose selected for ongoing development in patients with advanced solid tumors and lymphoma.

Experimental Design: A total of 346 patients with advanced cancers who had progressed after standard treatment received at least one dose of urelumab in one of three dose–escalation, monotherapy studies. Urelumab was administered at doses ranging from 0.1 to 15 mg/kg. Safety analyses included treatment-related and serious adverse events (AEs), as well as treatment-related AEs leading to discontinuation and death, with a focus on liver function test abnormalities and hepatic AEs.

Results: Urelumab doses between 1 and 15 mg/kg given every 3 weeks resulted in a higher frequency of treatment-related AEs than 0.1 or 0.3 mg/kg every 3 weeks. Dose was the single most important factor contributing to transaminitis development, which was more frequent and severe at doses ≥1 mg/kg. At the MTD of 0.1 mg/kg every 3 weeks, urelumab was relatively well tolerated, with fatigue (16%) and nausea (13%) being the most common treatment-related AEs, and was associated with immunologic and pharmacodynamic activity demonstrated by the induction of IFN-inducible genes and cytokines.

Conclusions: Integrated evaluation of urelumab safety data showed significant transaminitis was strongly associated with doses of ≥1 mg/kg. However, urelumab 0.1 mg/kg every 3 weeks was demonstrated to be safe, with pharmacodynamic activity supporting continued clinical evaluation of this dose as monotherapy and in combination with other immuno-oncology agents. Clin Cancer Res; 23(8); 1929–36. ©2016 AACR.
A Phase II, Randomized, Open-Label Study of Neoadjuvant Degarelix versus LHRH Agonist in Prostate Cancer Patients Prior to Radical Prostatectomy
Authors: Sayyid Rashid K. , Evans Andrew , Hersey Karen , Maloni Ranjena , Hurtado-Coll Antonio , Kulkarni Girish , Finelli Antonio , Zlotta Alexandre R. , Hamilton Robert , Gleave Martin , Fleshner Neil E.
Published: October 2016

Purpose: Degarelix, a new gonadotropin-releasing hormone (GnRH) receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over luteinizing hormone–releasing hormone (LHRH) analogues in terms of avoiding “testosterone flare” and lower follicle-stimulating hormone (FSH) levels. We set out to determine whether preoperative degarelix influenced surrogates of disease control in a randomized phase II study.

Experimental Design: Thirty-nine patients were randomly assigned to one of three different neoadjuvant arms: degarelix only, degarelix/bicalutamide, or LHRH agonist/bicalutamide. Treatments were given for 3 months before prostatectomy. Patients had localized prostate cancer and had chosen radical prostatectomy as primary treatment. The primary end point was treatment effect on intratumoral dihydrotestosterone levels.

Results: Intratumoral DHT levels were higher in the degarelix arm than both the degarelix/bicalutamide and LHRH agonist/bicalutamide arms (0.87 ng/g vs. 0.26 ng/g and 0.23 ng/g, P < 0.01). No significant differences existed for other intratumoral androgens, such as testosterone and dehydroepiandrosterone. Patients in the degarelix-only arm had higher AMACR levels on immunohistochemical analysis (P = 0.01). Serum FSH levels were lower after 12 weeks of therapy in both degarelix arms than the LHRH agonist/bicalutamide arm (0.55 and 0.65 vs. 3.65, P < 0.01), and inhibin B levels were lower in the degarelix/bicalutamide arm than the LHRH agonist/bicalutamide arm (82.14 vs. 126.67, P = 0.02).

Conclusions: Neoadjuvant degarelix alone, compared with use of LHRH agonist and bicalutamide, is associated with higher levels of intratumoral dihydrotestosterone, despite similar testosterone levels. Further studies that evaluate the mechanisms behind these results are needed. Clin Cancer Res; 23(8); 1974–80. ©2016 AACR.
Benefits of Multifaceted Chemopreventives in the Suppression of the Oral Squamous Cell Carcinoma (OSCC) Tumorigenic Phenotype
Authors: Mallery Susan R. , Wang Daren , Santiago Brian , Pei Ping , Schwendeman Steven P. , Nieto Kari , Spinney Richard , Tong Meng , Koutras George , Han Brian , Holpuch Andrew , Lang James
Published: October 2016

Over one third of patients who have undergone oral squamous cell carcinoma (OSCC) surgical resections develop life-threatening and often untreatable recurrences. A variety of drugs, intended for management of recurrent or disseminated cancers, were designed to exploit cancer cells' reliance upon overexpressed receptors and gratuitous signaling. Despite their conceptual promise, clinical trials showed these agents lacked efficacy and were often toxic. These findings are consistent with evasion of pathway-targeted treatments via extensive signaling redundancies and compensatory mechanisms common to cancers. Optimal secondary OSCC chemoprevention requires long-term efficacy with multifaceted, nontoxic agents. Accordingly, this study evaluated the abilities of three complementary chemopreventives, that is, the vitamin A derivative fenretinide (4-HPR, induces apoptosis and differentiation, inhibits signaling proteins, and invasion), the estrogen metabolite 2-methoxyestradiol (2-ME, apoptosis-inducing, antiangiogenic), and the humanized mAb to the IL6R receptor tocilizumab (TOC, reduces IL6 signaling) to suppress OSCC gratuitous signaling and tumorigenesis. Modeling studies demonstrated 4-HPR's high-affinity binding at STAT3′s dimerization site and c-Abl and c-Src ATP-binding kinase sites. Although individual agents suppressed cancer-promoting pathways including STAT3 phosphorylation, STAT3-DNA binding, and production of the trans-signaling enabling sIL6R, maximal chemopreventive effects were observed with agent combinations. OSCC tumor xenograft studies showed that locally delivered TOC, TOC+4-HPR, and TOC+4-HPR+2-ME treatments all prevented significant tumor growth. Notably, the TOC+4-HPR+2-ME treatment resulted in the smallest overall increase in tumor volume. The selected agents use diverse mechanisms to disrupt tumorigenesis at multiple venues, that is, intracellular, tumor cell-ECM, and tumor microenvironment; beneficial qualities for secondary chemopreventives. Cancer Prev Res; 10(1); 76–88. ©2016 AACR.
Response of the Nitric Oxide System to Hypobaric Hypoxia in the Aged Striatum
Authors: Molina Francisco , del Moral María Luisa , Peinado María Ángeles , Rus Alma
Published: October 2016

Background: Nitric oxide (NO) appears to play a key role in the hypoxic injury to the brain. We have previously reported that hypoxia/reoxygenation downregulated NO synthases (NOS) in the adult striatum. Until now, no data were available concerning the influence of aging in conjunction with hypoxia/reoxygenation on the NO system in the striatum. Objective: The aim of this study was to assess the role of the NO pathway in the hypoxic aged striatum. Methods: Wistar rats 24-25 months old were submitted to hypobaric hypoxia (20 min)/reoxygenation (0 h, 24 h, 5 days). Expression (PCR, immunohistochemistry/image analysis) and activity (NADPH-diaphorase/image analysis) of NOS isoforms (neuronal NOS or nNOS, endothelial NOS or eNOS, inducible NOS or iNOS) were analyzed together with nitrated protein expression (immunohistochemistry/image analysis). NO levels were indirectly quantified as nitrates/nitrites (NOx). Results: The mRNA levels of NOS isoforms were undetectable at 0 h after hypoxia in the striatum compared to the control. At later reoxygenation times, nNOS mRNA decreased, while eNOS mRNA augmented. Protein levels of nNOS and eNOS rose at 24 h after hypoxia, and iNOS protein increased at 5 days. NOx levels remained unchanged, whereas in situ NOS activity and protein nitration diminished during reoxygenation in the aged striatum. Conclusion: The aged striatum may overexpress NOS isoforms as a neuroprotective-adaptive mechanism to hypoxia. However, this mechanism may not work properly in the aged striatum, since no changes in NO levels were detected after hypoxia. This may be related to the low activity of NOS isoforms in the hypoxic striatum.