bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Papillomavirus 16 (HPV-16), HPV-18, and HPV-31 E6 Override the Normal Phosphoregulation of E6AP Enzymatic Activity
Authors: Thatte Jayashree , Banks Lawrence
Published: August 2017

The human papillomavirus (HPV) E6 oncoproteins recruit the cellular ubiquitin ligase E6AP/UBE3A to target cellular substrates for proteasome-mediated degradation, and one consequence of this activity is the E6 stimulation of E6AP autoubiquitination and degradation. Recent studies identified an autism-linked mutation within E6AP at T485, which was identified as a protein kinase A phosphoacceptor site and which could directly regulate E6AP ubiquitin ligase activity. In this study, we have analyzed how T485-mediated regulation of E6AP might affect E6 targeting of some of its known substrates. We show that modulation of T485 has no effect on the ability of E6 to direct either p53 or Dlg for degradation. Furthermore, T485 regulation has no effect on HPV-16 or HPV-31 E6-induced autodegradation of E6AP but does affect HPV-18 E6-induced autodegradation of E6AP. In cells derived from cervical cancers, we find low levels of both phosphorylated and nonphosphorylated E6AP in the nucleus. However, ablation of E6 results in a dramatic accumulation of phospho-E6AP in the cytoplasm, whereas nonphosphorylated E6AP accumulates primarily in the nucleus. Interestingly, E6AP phosphorylation at T485 confers association with 14-3-3 proteins, and this interaction seems to be important, in part, for the ability of E6 to recruit phospho-E6AP into the nucleus. These results demonstrate that HPV E6 overrides the normal phosphoregulation of E6AP, both in terms of its enzymatic activity and its subcellular distribution.

IMPORTANCE
Recent reports demonstrate the importance of phosphoregulation of E6AP for its normal enzymatic activity. Here, we show that HPV E6 is capable of overriding this regulation and can promote degradation of p53 and Dlg regardless of the phosphorylation status of E6AP. Furthermore, E6 interaction with E6AP also significantly alters how E6AP is subject to autodegradation and suggests that this is not a simple stimulation of an already-existing activity but rather a redirection of E6AP activity toward itself. Furthermore, E6-mediated regulation of the subcellular distribution of phospho-E6AP appears to be dependent, in part, upon the 14-3-3 family of proteins.
The Microtubule-Stabilizing Protein CLASP1 Associates with the
Theileria annulata
Schizont Surface via Its Kinetochore-Binding Domain
Authors: Huber Sandra , Theiler Romina , de Quervain Daniel , Wiens Olga , Karangenc Tulin , Heussler Volker , Dobbelaere Dirk , Woods Kerry
Published: August 2017

T. annulata
, the only eukaryote known to be capable of transforming another eukaryote, is a widespread parasite of veterinary importance that puts 250 million cattle at risk worldwide and limits livestock development for some of the poorest people in the world. Crucial to the pathology of
Theileria
is its ability to interact with host microtubules and the mitotic spindle of the infected cell. This study builds on our previous work in investigating the host and parasite molecules involved in mediating this interaction. Because it is not possible to genetically manipulate
Theileria
schizonts, identifying protein interaction partners is critical to understanding the function of parasite proteins. By identifying two
Theileria
surface proteins that are involved in the interaction between CLASP1 and the parasite, we provide important insights into the molecular basis of
Theileria
persistence within a dividing cell.
Options for Synthetic DNA Order Screening, Revisited
Authors: DiEuliis Diane , Carter Sarah R. , Gronvall Gigi Kwik
Published: August 2017

Gene synthesis providers affiliated with the International Gene Synthesis Consortium (IGSC) voluntarily screen double-stranded DNA (dsDNA) synthesis orders over 200 bp to check for matches to regulated pathogens and to screen customers. Questions have been raised, however, about the continuing feasibility and effectiveness of screening.
Monodeuterated Methane, an Isotopic Tool To Assess Biological Methane Metabolism Rates
Authors: Marlow Jeffrey J. , Steele Joshua A. , Ziebis Wiebke , Scheller Silvan , Case David , Reynard Linda M. , Orphan Victoria J.
Published: August 2017

Microbial methane consumption is a critical component of the global carbon cycle, with wide-ranging implications for climate regulation and hydrocarbon exploitation. Nonetheless, quantifying methane metabolism typically involves logistically challenging methods and/or specialized equipment; these impediments have limited our understanding of methane fluxes and reservoirs in natural systems, making effective management difficult. Here, we offer an easily implementable, precise method using monodeuterated methane (CH
3
D) that advances three specific aims. First, it allows users to directly compare methane consumption rates between different experimental treatments of the same inoculum. Second, by empirically linking the CH
3
D procedure with the well-established
14
C radiocarbon approach, we determine absolute scaling factors that facilitate rate measurements for several aerobic and anaerobic systems of interest. Third, CH
3
D represents a helpful tool in evaluating the relationship between methane activation and full oxidation in methanotrophic metabolisms. The procedural advantages, consistency, and novel research questions enabled by the CH
3
D method should prove useful in a wide range of culture-based and environmental microbial systems to further elucidate methane metabolism dynamics.
Hepatic artery aneurysm: an unusual cause of upper gastrointestinal bleed
Authors: Frank Madeleine , Phillips Rosemary , Aldin Zaid , Ghosh Deb
Published: August 2017

An 86-year-old woman presented to hospital with melaena. This was her third presentation with the same symptom. There was no obvious source of bleeding on her oesophagogastroduodenoscopy; however, it did show a previously clipped Dieulafoy lesion. CT angiography showed an aneurysm arising from the hepatic artery. Selective coeliac artery angiogram showed aneurysmal dilatation of the distal part of the coeliac trunk and confirmed the presence of the common hepatic artery aneurysm. The aneurysm was coiled by the interventional radiologist. Final angiogram showed good flow through the hepatic artery with obliteration of the inferior patch. The procedure was uncomplicated and the patient was discharged shortly afterwards.
A correlated structural and electrical study of manganese ferrite nanoparticles with variation in sintering temperature
Authors: Devi Elangbam Chitra , Soibam Ibetombi
Published: August 2017

Manganese ferrite nanoparticles were prepared by chemical co-precipitation method. Metal chlorides and sodium hydroxide were used as precursor. The spinel phase formation of the prepared samples was confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). From the XRD data, the average crystallite size and lattice constant were calculated. FTIR spectra reveal the characteristic absorption bands of spinel ferrite due to M-O stretching vibrations in tetrahedral and octahedral sites. Manganese ferrite nanoparticles were further given sintering. The effect of sintering at different temperatures on the structural properties such as XRD, FTIR and electrical properties such as dielectric constant, dielectric loss and ac-conductivity was studied. Possible mechanism of structural changes and observed electrical behavior due to sintering is being discussed. A strong correlation has also been observed in the results obtained from different characterization techniques.
Constrained-Energy Dynamic Cross-Well Motion of Bistable Structures Subjected to Noise Disturbance
Authors: Zarepoor Masoud , Bilgen Onur
Published: August 2017

Bistable structures have two stable equilibrium positions and can be utilized to maintain a static shape with no energy consumption. This paper focuses on the minimum energy required for performing snap-through of a bistable structure subjected to noise disturbance. This paper uses the Duffing–Holmes equation as a one-degree-of-freedom representative model of a bistable structure. This equation is numerically solved to calculate the energy required for cross-well oscillation under different system and forcing conditions. The paper shows how the energy required for cross-well transfer varies as a function of damping ratio and frequency ratio at specific harmonic force amplitude when the system is externally disturbed with a band-limited noise signal. A magneto-elastic bistable beam is fabricated and tested to validate the used mathematical model. Various nondimensional parameters are used to highlight interesting phenomena. The relationships between signal-to-noise ratio (SNR), dynamic-to-static force ratio, and damping ratio to the response behavior are shown. It is found that the domain of low energy regions decreases by increasing the level of noise. Additionally, underactuated bistable and linear systems behave similarly for high levels of noise. This paper specifically identifies the critical force ratio, which allows for snap-through as a function of critical nondimensional system parameters.
Free Vibration and Buckling Analysis of Functionally Graded Plates Resting on Elastic Foundation Using Higher Order Theory
Authors: Parida Smita , Mohanty Sukesh Chandra
Published: August 2017

This paper deals with the free vibration and buckling analysis of functionally graded material (FGM) plates, resting on the Winkler–Pasternak elastic foundation. The higher order shear deformation plate theory (HSPT) is adopted for the realistic variation of transverse displacement through the thickness, using the power law distribution to describe the variation of the material properties. Both the effects of shear deformation and rotary inertia are considered. In the present model, the plate is discretised into [Formula: see text] eight noded serendipity quadratic elements with seven nodal degrees of freedom (DOFs). The validation study is carried out by comparing the calculated values with those given in the literature. The effects of various parameters like the Winkler and Pasternak modulus coefficients, volume fraction index, aspect ratio, thickness ratio and different boundary conditions on the behaviour of the FGM plates are studied.
Nonlinear Vibration of Size Dependent Microresonators with an Electrostatically Actuated Proof Mass
Authors: Sharifinsab Ehsan , Mojahedi Mahdi
Published: August 2017

In this paper, the dynamic and nonlinear vibration responses of a microresonator containing a microbridge with a proof mass located at its middle are studied. The proof mass of the microresonator is actuated by the electrostatic field in such a way that a direct voltage finds a certain equilibrium position and then be prompted to vibration under the alternative voltage. Due to the importance of the size dependency effect in analysis of the performance of microelectromechanical systems, the size dependent theory is used in the modeling of the microstructure. By adopting the modified couple stress theory and considering electrostatic actuation, the dynamic equation of motion is derived using the extended Hamilton’s principle. Further, with the approximation by Galerkin’s method, the governing equation for the static and oscillatory motion is reduced and the resultant equation is solved by analytical (multiple-scales) and numerical methods. In the analytical and numerical results, the effects of various parameters on the system response, including the midplane stretching and size dependent effects, and dependency of vibration response to initial conditions, are analyzed in detail.
Hyperbolic groups with boundary an n-dimensional Sierpinski space
Authors: Lafont Jean-François , Tshishiku Bena
Published: August 2017

For [Formula: see text], we show that if [Formula: see text] is a torsion-free hyperbolic group whose visual boundary [Formula: see text] is an [Formula: see text]-dimensional Sierpinski space, then [Formula: see text] for some aspherical [Formula: see text]-manifold [Formula: see text] with non-empty boundary. Concerning the converse, we construct, for each [Formula: see text], examples of aspherical manifolds with boundary, whose fundamental group [Formula: see text] is hyperbolic, but with visual boundary [Formula: see text] not homeomorphic to [Formula: see text]. Our examples even support (metric) negative curvature, and have totally geodesic boundary.
The Role of Information and Knowledge in Achieving Environmentally Sound Farming: A Chinese Case
Authors: ORDERUD Geir Inge , VOGT Rolf D. , TAN Hongze , LUO Jing
Published: August 2017

The paper analyzes the role of information–knowledge for making farming environmentally friendly, using eutrophication of the main drinking water reservoir of Tianjin, China as a case. The analysis considers information and instruction sources used by farmers in relation to their farming and environmental issues, in particular application of fertilizers, and on this basis it discusses governance and policy measures. The study is interdisciplinary, covering both natural and social sciences, and it is based on quantitative methodology, employing descriptive and multivariate statistical methods. The main findings are: (i) farmers make use of a broad range of information and instruction sources, thereby confirming the claim that eutrophication and hence good farming practices are a “wicked” problem; (ii) the young and the members of the Communist Party are more active than others in using a broad range of information and instruction sources; (iii) different categories of farmers give priority to different information and instruction sources, providing a basis for tailor-made disseminations; (iv) the majority of farmers report receiving clear instructions for using fertilizers, yet half of them conceive using fertilizers correctly as difficult; (v) receiving instructions from other farmers and suppliers cater for high scores on clear instructions; and (vi) farmers are best seen as muddling through different pressures from above and different knowledge bases, and not just willy-nilly responding to top-down policy instructions.
Reliability or Sustainability
Authors: Kartakis Sokratis , Yang Shusen , Mccann Julie A.
Published: August 2017

As a typical cyber-physical system (CPS), smart water distribution networks require monitoring of underground water pipes with high sample rates for precise data analysis and water network control. Due to poor underground wireless channel quality and long-range communication requirements, high transmission power is typically adopted to communicate high-speed sensor data streams, posing challenges for long-term sustainable monitoring. In this article, we develop the first sustainable water sensing system, exploiting energy harvesting opportunities from water flows. Our system does this by scheduling the transmission of a subset of the data streams, whereas other correlated streams are estimated using autoregressive models based on the sound-velocity propagation of pressure signals inside water networks. To compute the optimal scheduling policy, we formalize a stochastic optimization problem to maximize the estimation reliability while ensuring the system’s sustainable operation under dynamic conditions. We develop data transmission scheduling (DTS), an asymptotically optimal scheme, and FAST-DTS, a lightweight online algorithm that can adapt to arbitrary energy and correlation dynamics. Using more than 170 days of real data from our smart water system deployment and conducting in vitro experiments to our small-scale testbed, our evaluation demonstrates that Fast-DTS significantly outperforms three alternatives, considering data reliability, energy utilization, and sustainable operation.
Bandwidth Measurements within the Cloud
Authors: García-Dorado José Luis
Published: August 2017

The search for availability, reliability, and quality of service has led cloud infrastructure customers to disseminate their services, contents, and data over multiple cloud data centers, often involving several Cloud service providers (CSPs). The consequence of this is that a large amount of data must be transmitted across the public Cloud. However, little is known about the bandwidth dynamics involved. To address this, we have conducted a measurement campaign for bandwidth between 18 data centers of four major CSPs. This extensive campaign allowed us to characterize the resulting time series of bandwidth as the addition of a stationary component and some infrequent excursions (typically downtimes). While the former provides a description of the bandwidth users can expect in the Cloud, the latter is closely related to the robustness of the Cloud (i.e., the occurrence of downtimes is correlated). Both components have been studied further by applying factor analysis, specifically analysis of variance, as a mechanism to formally compare data centers’ behaviors and extract generalities. The results show that the stationary process is closely related to the data center locations and CSPs involved in transfers that, fortunately, make the Cloud more predictable and allow the set of reported measurements to be extrapolated. On the other hand, although correlation in the Cloud is low, that is, only 10% of the measured pair of paths showed some correlation, we found evidence that such correlation depends on the particular relationships between pairs of data centers with little connection to more general factors. Positively, this implies that data centers either in the same area or within the same CSP do not show qualitatively more correlation than other data centers, which eases the deployment of robust infrastructures. On the downside, this metric is scarcely generalizable and, consequently, calls for exhaustive monitoring.
A Supervised Learning Approach for Authorship Attribution of Bengali Literary Texts
Authors: Phani Shanta , Lahiri Shibamouli , Biswas Arindam
Published: August 2017

Authorship Attribution is a long-standing problem in Natural Language Processing. Several statistical and computational methods have been used to find a solution to this problem. In this article, we have proposed methods to deal with the authorship attribution problem in Bengali. More specifically, we proposed a supervised framework consisting of lexical and shallow features and investigated the possibility of using topic-modeling-inspired features, to classify documents according to their authors. We have created a corpus from nearly all the literary works of three eminent Bengali authors, consisting of 3,000 disjoint samples. Our models showed better performance than the state-of-the-art, with more than 98% test accuracy for the shallow features and 100% test accuracy for the topic-based features. Further experiments with GloVe vectors [Pennington et al. 2014] showed comparable results, but flexible patterns based on content words and high-frequency words [Schwartz et al. 2013] failed to perform as well as expected.
It's all about image
Authors: Greengard Samuel
Published: August 2017

Image recognition technology is advancing rapidly. Researchers are discovering new ways to tackle the task without enormous datasets.
Charles W. Bachman
Authors: Fisher Lawrence M.
Published: August 2017

An engineer best known for his work in database management systems, and in techniques of layered architecture that include Bachman diagrams.
Platelet CLEC-2 protects against lung injury via effects of its ligand podoplanin on inflammatory alveolar macrophages in the mouse
Authors: Lax Siân , Rayes Julie , Wichaiyo Surasak , Haining Elizabeth J. , Lowe Kate , Grygielska Beata , Laloo Ryan , Flodby Per , Borok Zea , Crandall Edward D. , Thickett David R. , Watson Steve P.
Published: August 2017

There is no therapeutic intervention proven to prevent acute respiratory distress syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes that occur during ARDS; however, the mechanisms remain elusive. The platelet receptor CLEC-2 has been shown to regulate vascular integrity at sites of acute inflammation. Therefore the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS. Platelet-specific CLEC-2-deficient, as well as alveolar epithelial type I cell (AECI)-specific or hematopoietic-specific podoplanin deficient, mice were established using cre-loxP strategies. Combining these with intratracheal (IT) instillations of lipopolysaccharide (LPS), we demonstrate that arterial oxygen saturation decline in response to IT-LPS in platelet-specific CLEC-2-deficient mice is significantly augmented. An increase in bronchoalveolar lavage (BAL) neutrophils and protein was also observed 48 h post-IT-LPS, with significant increases in pro-inflammatory chemokines detected in BAL of platelet-specific CLEC-2-deficient animals. Deletion of podoplanin from hematopoietic cells but not AECIs also reduces lung function and increases pro-inflammatory chemokine expression following IT-LPS. Furthermore, we demonstrate that following IT-LPS, platelets are present in BAL in aggregates with neutrophils, which allows for CLEC-2 interaction with podoplanin expressed on BAL inflammatory alveolar macrophages. Taken together, these data suggest that the platelet CLEC-2-podoplanin signaling axis regulates the severity of lung inflammation in mice and is a possible novel target for therapeutic intervention in patients at risk of developing ARDS.
Alcohol abuse is associated with enhanced pulmonary and systemic xanthine oxidoreductase activity
Authors: Fini Mehdi A. , Gaydos Jeanette , McNally Alicia , Karoor Vijaya , Burnham Ellen L.
Published: August 2017

Acute respiratory distress syndrome (ARDS) is a common and devastating disorder. Alcohol use disorders (AUDs) increase ARDS risk and worsen outcomes through mechanisms that may include enhancement of pulmonary oxidative stress. Alcohol consumption increases activity of the enzyme xanthine oxidoreductase (XOR) that contributes to production of both reactive oxygen species (ROS) and uric acid, a damage-associated molecular pattern. These by-products have the potential to modulate proinflammatory pathways, such as those involving cyclooxygenase (COX)-2, and to activate the nucleotide-binding domain, leucine-rich-containing family, pyrin-domain containing-3 (NLRP3) inflammasome. We sought to determine if pulmonary and systemic XOR activity was altered by AUDs. Bronchoscopy with bronchoalveolar lavage (BAL) and blood sampling was performed in otherwise healthy human subjects with AUDs and controls. Uric acid in epithelial-lining fluid, derived from BAL, was substantially higher among individuals with AUDs and did not normalize after 7 days of abstinence; serum uric acid did not differ across groups. XOR enzyme activity in fresh BAL cells and serum was significantly increased in subjects with AUDs. XOR protein in BAL cells from AUD subjects was increased in parallel with COX-2 expression, and furthermore, mRNA expression of NLRP3 inflammasome components was sustained in LPS-stimulated BAL cells from AUD subjects in conjunction with increased IL-1β. Our data suggest that AUDs augment pulmonary and systemic XOR activity that may contribute to ROS and uric acid generation, promoting inflammation. Further investigations will be necessary to determine if XOR inhibition can mitigate alcohol-associated pulmonary oxidative stress, diminish inflammation, and improve ARDS outcomes.
Acute hypoxia in a simulated high-altitude airdrop scenario due to oxygen system failure
Authors: Ottestad William , Hansen Tor Are , Pradhan Gaurav , Stepanek Jan , Høiseth Lars Øivind , Kåsin Jan Ivar
Published: August 2017

High-Altitude High Opening (HAHO) is a military operational procedure in which parachute jumps are performed at high altitude requiring supplemental oxygen, putting personnel at risk of acute hypoxia in the event of oxygen equipment failure. This study was initiated by the Norwegian Army to evaluate potential outcomes during failure of oxygen supply, and to explore physiology during acute severe hypobaric hypoxia. A simulated HAHO without supplemental oxygen was carried out in a hypobaric chamber with decompression to 30,000 ft (9,144 m) and then recompression to ground level with a descent rate of 1,000 ft/min (305 m/min). Nine subjects were studied. Repeated arterial blood gas samples were drawn throughout the entire hypoxic exposure. Additionally, pulse oximetry, cerebral oximetry, and hemodynamic variables were monitored. Desaturation evolved rapidly and the arterial oxygen tensions are among the lowest ever reported in volunteers during acute hypoxia. PaO2 decreased from baseline 18.4 (17.3–19.1) kPa, 138.0 (133.5–143.3) mmHg, to a minimum value of 3.3 (2.9–3.7) kPa, 24.8 (21.6–27.8) mmHg, after 180 (60–210) s, [median (range)], N = 9. Hyperventilation with ensuing hypocapnia was associated with both increased arterial oxygen saturation and cerebral oximetry values, and potentially improved tolerance to severe hypoxia. One subject had a sharp drop in heart rate and cardiac index and lost consciousness 4 min into the hypoxic exposure. A simulated high-altitude airdrop scenario without supplemental oxygen results in extreme hypoxemia and may result in loss of consciousness in some individuals.

NEW & NOTEWORTHY This is the first study to investigate physiology and clinical outcome of oxygen system failure in a simulated HAHO scenario. The acquired knowledge is of great value to make valid risk-benefit analyses during HAHO training or operations. The arterial oxygen tensions reported in this hypobaric chamber study are among the lowest ever reported during acute hypoxia.
Quantal Fluctuations in Central Mammalian Synapses: Functional Role of Vesicular Docking Sites
Authors: Pulido Camila , Marty Alain
Published: August 2017

Quantal fluctuations are an integral part of synaptic signaling. At the frog neuromuscular junction, Bernard Katz proposed that quantal fluctuations originate at “reactive sites” where specific structures of the presynaptic membrane interact with synaptic vesicles. However, the physical nature of reactive sites has remained unclear, both at the frog neuromuscular junction and at central synapses. Many central synapses, called simple synapses, are small structures containing a single presynaptic active zone and a single postsynaptic density of receptors. Several lines of evidence indicate that simple synapses may release several synaptic vesicles in response to a single action potential. However, in some synapses at least, each release event activates a significant fraction of the postsynaptic receptors, giving rise to a sublinear relation between vesicular release and postsynaptic current. Partial receptor saturation as well as synaptic jitter gives to simple synapse signaling the appearance of a binary process. Recent investigations of simple synapses indicate that the number of released vesicles follows binomial statistics, with a maximum reflecting the number of docking sites present in the active zone. These results suggest that at central synapses, vesicular docking sites represent the reactive sites proposed by Katz. The macromolecular architecture and molecular composition of docking sites are presently investigated with novel combinations of techniques. It is proposed that variations in docking site numbers are central in defining intersynaptic variability and that docking site occupancy is a key parameter regulating short-term synaptic plasticity.
Testosterone Upregulates the Expression of Mitochondrial ND1 and ND4 and Alleviates the Oxidative Damage to the Nigrostriatal Dopaminergic System in Orchiectomized Rats
Authors: Yan Wensheng , Kang Yunxiao , Ji Xiaoming , Li Shuangcheng , Li Yingkun , Zhang Guoliang , Cui Huixian , Shi Geming
Published: August 2017

Testosterone deficiency, as a potential risk factor for aging and aging‐related neurodegenerative disorders, might induce mitochondrial dysfunction and facilitate the declines of the nigrostriatal dopaminergic system by exacerbating the mitochondrial defects and increasing the oxidative damage. Thus, how testosterone levels influence the mitochondrial function in the substantia nigra was investigated in the study. The present studies showed that testosterone deficiency impaired the mitochondrial function in the substantia nigra and induced the oxidative damage to the substantia nigra as well as the deficits in the nigrostriatal dopaminergic system. Of four mitochondrial respiratory chain complexes, castration of male rats reduced the activity of mitochondrial complex I and downregulated the expression of ND1 and ND4 of 7 mitochondrial DNA‐ (mtDNA‐) encoded subunits of complex I in the substantia nigra. Supplements of testosterone propionate to castrated male rats ameliorated the activity of mitochondrial complex I and upregulated the expression of mitochondrial ND1 and ND4. These results suggest an important role of testosterone in maintaining the mitochondrial function in the substantia nigra and the vulnerability of mitochondrial complex I to testosterone deficiency. Mitochondrial ND1 and ND4, as potential testosterone targets, were implicated in the oxidative damage to the nigrostriatal dopaminergic system.
The Beneficial Effects of Quercetin, Curcumin, and Resveratrol in Obesity
Authors: Zhao Yueshui , Chen Bo , Shen Jing , Wan Lin , Zhu Yinxin , Yi Tao , Xiao Zhangang
Published: August 2017

Over the past two decades, obesity has been one of the major public health concerns in most countries. In the search for new molecules that could be used for the treatment of obesity, good perspectives have been opened up for polyphenols, a class of natural bioactive phytochemicals. Experimental and limited clinical trial evidence supports that some polyphenols such as quercetin, curcumin, and resveratrol have potential benefit functions on obesity treatment. This brief review focuses on the main functions of the above‐named polyphenols on adipose tissue. These polyphenols may play beneficial effects on adipose tissue under obese condition by alleviating intracellular oxidative stress, reducing chronic low‐grade inflammation, inhibiting adipogenesis and lipogenesis, and suppressing the differentiation of preadipocytes to mature adipocytes.
The “e-Generation”: The Technological Usage and Experiences of Medical Students from a Developing Country
Authors: Galappatthy Priyasdarshani , Wathurapatha Wasundara S. , Ranasinghe Priyanga , Wijayabandara Maheshi D. M. S. , Warapitiya Dinuka S. , Weerasuriya Krishantha
Published: August 2017

Background. The medical community is increasingly using Portable Electronic Devices (PEDs). We evaluated usage of PEDs and medical apps among medical students from Sri Lanka. Methods. This descriptive cross-sectional study was conducted at Faculty of Medicine, University of Colombo. Medical students from 2nd to 5th year were invited for the study. A self-administered questionnaire was used to collect details of PEDs availability, accessibility, and usage, perceived advantages/barriers of PEDs, and availability, accessibility, and usage of medical apps. Results. Sample size was 505 (response rate, 61.8%). Mean age was 23.2±1.3 years and majority were females (60.4%, n=305). Majority (87.5%, n=442) of students owned a PED. Nonaffordability was the most common reason for having not owning a PED (46%). Nonaffordability and lack of knowledge were key determinants of the usage of PEDs and medical “apps.” Doubts about reliability and lack of knowledge regarding reliable electronic sources of information were other significant barriers. Conclusions. Our results show that a significant majority of students owned a PED, a higher percentage than what is reported elsewhere. Considering barriers identified, it is important for institutions to promote usage of PEDs and medical apps by providing financial support, training, and knowledge to build confidence in technology.
A Novel Fifth‐Degree Cubature Kalman Filter for Real‐Time Orbit Determination by Radar
Authors: Li Zhaoming , Yang Wenge , Ding Dan , Liao Yurong
Published: August 2017

A novel fifth‐degree cubature Kalman filter is proposed to improve the accuracy of real‐time orbit determination by ground‐based radar. A fully symmetric cubature rule, approaching the Gaussian weighted integral of a nonlinear function in general form, is introduced, and the specific points and weights are calculated by matching the monomials of degree not greater than five with the exact values. On the basis of the above rule, a novel fifth‐degree cubature Kalman filter, which can achieve a higher accuracy than UKF and CKF, is derived under the Bayesian filtering framework. Then, to describe the nonlinear system more accurately, the orbital dynamics equation with J2 perturbation is used as the state equation, and the nonlinear relationship between the radar measurement elements and orbital states is built as the measurement equation. The simulation results show that, compared with the traditional third‐degree algorithm, the proposed fifth‐degree algorithm has a higher accuracy of orbit determination.
Investigations on the Occurrence and Associated Risk Factors of Avian Coccidiosis in Osun State, Southwestern Nigeria
Authors: Ola-Fadunsin Shola David
Published: August 2017

Avian coccidiosis is one of the most important diseases of poultry and it is responsible for a large number of poultry mortalities worldwide. This study was carried out to investigate the occurrence and associated risk factors of avian coccidiosis in Osun State, Nigeria. Fecal samples were collected and examined from 5,544 avian species that were brought for treatment at the state veterinary hospitals over a 10-year period. Parameters such as age, sex, season, and species of birds were determined. Also, the months of the year were taken into consideration. Overall prevalence of 41.3% was recorded. The year specific rate for avian coccidiosis was highest in 2007 (97.9%) and lowest in 2006 (0.4%), while the month-specific rate was highest in November (85.7%) and lowest in July 2006 (13.3%). There was a significantly (P<0.05) higher prevalence in young birds compared to adults, in males compared to females, and during the wet season compared to the dry season. Broilers (99.8%) and cockerels (81.0%) were the bird types with the highest prevalence rate. The high prevalence of avian coccidiosis in the study area shows that the disease is endemic and there is need to embark on a radical preventive measure to curtail the disease.
Targeting Phosphatidylinositol 3-Kinase Signaling Pathway for Therapeutic Enhancement of Vascular-Targeted Photodynamic Therapy
Authors: Kraus Daniel , Palasuberniam Pratheeba , Chen Bin
Published: August 2017

Vascular-targeted photodynamic therapy (PDT) selectively disrupts vascular function by inducing oxidative damages to the vasculature, particularly endothelial cells. Although effective tumor eradication and excellent safety profile are well demonstrated in both preclinical and clinical studies, incomplete vascular shutdown and angiogenesis are known to cause tumor recurrence after vascular-targeted PDT. We have explored therapeutic enhancement of vascular-targeted PDT with PI3K signaling pathway inhibitors because the activation of PI3K pathway was involved in promoting endothelial cell survival and proliferation after PDT. Here, three clinically relevant small-molecule inhibitors (BYL719, BKM120, and BEZ235) of the PI3K pathway were evaluated in combination with verteporfin-PDT. Although all three inhibitors were able to synergistically enhance PDT response in endothelial cells, PDT combined with dual PI3K/mTOR inhibitor BEZ235 exhibited the strongest synergism, followed in order by combinations with pan-PI3K inhibitor BKM120 and p110α isoform-selective inhibitor BYL719. Combination treatments of PDT and BEZ235 exhibited a cooperative inhibition of antiapoptotic Bcl-2 family protein Mcl-1 and induced more cell apoptosis than each treatment alone. In addition to increasing treatment lethality, BEZ235 combined with PDT effectively inhibited PI3K pathway activation and consequent endothelial cell proliferation after PDT alone, leading to a sustained growth inhibition. In the PC-3 prostate tumor model, combination treatments improved treatment outcomes by turning a temporary tumor regrowth delay induced by PDT alone to a more long-lasting treatment response. Our study strongly supports the combination of vascular-targeted PDT and PI3K pathway inhibitors, particularly mTOR inhibitors, for therapeutic enhancement. Mol Cancer Ther; 16(11); 2422–31. ©2017 AACR.
Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers
Authors: Goodman Aaron M. , Kato Shumei , Bazhenova Lyudmila , Patel Sandip P. , Frampton Garrett M. , Miller Vincent , Stephens Philip J. , Daniels Gregory A. , Kurzrock Razelle
Published: August 2017

Immunotherapy induces durable responses in a subset of patients with cancer. High tumor mutational burden (TMB) may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non–small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. We reviewed data on 1,638 patients who had undergone comprehensive genomic profiling and had TMB assessment. Immunotherapy-treated patients (N = 151) were analyzed for response rate (RR), progression-free survival (PFS), and overall survival (OS). Higher TMB was independently associated with better outcome parameters (multivariable analysis). The RR for patients with high (≥20 mutations/mb) versus low to intermediate TMB was 22/38 (58%) versus 23/113 (20%; P = 0.0001); median PFS, 12.8 months vs. 3.3 months (P ≤ 0.0001); median OS, not reached versus 16.3 months (P = 0.0036). Results were similar when anti-PD-1/PD-L1 monotherapy was analyzed (N = 102 patients), with a linear correlation between higher TMB and favorable outcome parameters; the median TMB for responders versus nonresponders treated with anti-PD-1/PD-L1 monotherapy was 18.0 versus 5.0 mutations/mb (P < 0.0001). Interestingly, anti-CTLA4/anti-PD-1/PD-L1 combinations versus anti-PD-1/PD-L1 monotherapy was selected as a factor independent of TMB for predicting better RR (77% vs. 21%; P = 0.004) and PFS (P = 0.024). Higher TMB predicts favorable outcome to PD-1/PD-L1 blockade across diverse tumors. Benefit from dual checkpoint blockade did not show a similarly strong dependence on TMB. Mol Cancer Ther; 16(11); 2598–608. ©2017 AACR.
Deep Brain Stimulation for the Treatment of Dejerine-Roussy Syndrome
Authors: Ward Max , Mammis Antonios
Published: August 2017

Background/Aims: Patients who suffer from Dejerine-Roussy syndrome commonly experience severe poststroke hemibody pain which has historically been attributed to thalamic lesions. Despite pharmacological treatment, a significant proportion of the population is resistant to traditional therapy. Deep brain stimulation is often appropriate for the treatment of resistant populations. In this review we aim to summarize the targets that are used to treat Dejerine-Roussy syndrome and provide insight into their clinical efficacy. Methods: In reviewing the literature, we defined stimulation success as achievement of a minimum of 50% pain relief. Results: Contemporary targets for deep brain stimulation are the ventral posterior medial/ventral posterior lateral thalamic nuclei, periaqueductal/periventricular gray matter, the ventral striatum/anterior limb of the internal capsule, left centromedian thalamic nuclei, the nucleus ventrocaudalis parvocellularis internis, and the posterior limb of the internal capsule. Conclusions: Due to technological advancements in deep brain stimulation, its therapeutic effects must be reevaluated. Despite a lack of controlled evidence, deep brain stimulation has been effectively used as a therapeutic in clinical pain management. Further clinical investigation is needed to definitively evaluate the therapeutic efficacy of deep brain stimulation in treating the drug-resistant patient population.
A Brain Phenotype for Stressor‐Evoked Blood Pressure Reactivity
Authors: Gianaros Peter J. , Sheu Lei K. , Uyar Fatma , Koushik Jayanth , Jennings J. Richard , Wager Tor D. , Singh Aarti , Verstynen Timothy D.
Published: August 2017

Background

Individuals who exhibit large‐magnitude blood pressure (
BP
) reactions to acute psychological stressors are at risk for hypertension and premature death by cardiovascular disease. This study tested whether a multivariate pattern of stressor‐evoked brain activity could reliably predict individual differences in
BP
reactivity, providing novel evidence for a candidate neurophysiological source of stress‐related cardiovascular risk.

Methods and Results

Community‐dwelling adults (N=310; 30–51 years; 153 women) underwent functional magnetic resonance imaging with concurrent
BP
monitoring while completing a standardized battery of stressor tasks. Across individuals, the battery evoked an increase systolic and diastolic
BP
relative to a nonstressor baseline period (M ∆systolic BP/∆diastolic BP=4.3/1.9 mm Hg [95% confidence interval=3.7–5.0/1.4–2.3 mm Hg]). Using cross‐validation and machine learning approaches, including dimensionality reduction and linear shrinkage models, a multivariate pattern of stressor‐evoked functional magnetic resonance imaging activity was identified in a training subsample (N=206). This multivariate pattern reliably predicted both systolic BP (
r
=0.32;
P
<0.005) and diastolic BP (
r
=0.25;
P
<0.01) reactivity in an independent subsample used for testing and replication (N=104). Brain areas encompassed by the pattern that were strongly predictive included those implicated in psychological stressor processing and cardiovascular responding through autonomic pathways, including the medial prefrontal cortex, anterior cingulate cortex, and insula.

Conclusions

A novel multivariate pattern of stressor‐evoked brain activity may comprise a phenotype that partly accounts for individual differences in
BP
reactivity, a stress‐related cardiovascular risk factor.
No Excuses Charter Schools and College Enrollment: New Evidence from a High School Network in Chicago
Authors: Davis Matthew , Heller Blake
Published: August 2017

Although it is well known that certain charter schools dramatically increase students' standardized test scores, there is considerably less evidence that these human capital gains persist into adulthood. To address this matter, we match three years of lottery data from a high-performing charter high school to administrative college enrollment records and estimate the effect of winning an admissions lottery on college matriculation, quality, and persistence. Seven to nine years after the lottery, we find that lottery winners are 10.0 percentage points more likely to attend college and 9.5 percentage points more likely to enroll for at least four semesters. Unlike previous studies, our estimates are powerful enough to uncover improvements on the extensive margin of college attendance (enrolling in any college), the intensive margin (persistence of attendance), and the quality margin (enrollment at selective, four-year institutions). We conclude by providing nonexperimental evidence that more recent cohorts at other campuses in the network increased enrollment at a similar rate.
Creativity in Chinese Schools
Authors: Mullen Carol A.
Published: August 2017

Is creativity occurring in China’s primary and secondary schools? The thesis undergirding this article is that creativity is a paradox and possibility within this test-centric culture. Discussion is of the literature on creativity from an international perspective, with support from an original pilot study. The Chinese schools visited arose out of an inquiry into crucial issues in basic education involving high-stakes accountability and effects on the creativity and innovation of children and youth. Pursuing knowledge in action, the u.s. Fulbright Scholar used observation, conversation, and interviews to explore creative processes in five rural and urban preK-12 schools within Southwest China. A teacher training institute confirmed that creative learning transpires within some of the primary schools in the region. Analyses of the data collected suggest the potential for creativity in schooling to co-exist with external accountability. These emergent results offer a lens for understanding intriguing developments of schooling in Chinese education.
Will the sup be an Effective Legal Form for smes as Well as for Subsidiaries within the European Union?
Authors: Boschma Hylda , Schutte-Veenstra Hanny
Published: August 2017

In 2014, the Commission published a proposal for a Directive that introduces a single- member private limited liability company, under a common label: Societas Unius Personae (sup), into the national legislation of the eu-Member States. In this publication it is examined what kind of legal forms of capital companies already exist in the eu-Member States and whether the sup is a welcome addition. The proposed legal form of the sup is analysed in order to answer the question whether the sup is an appropriate legal form for smes and subsidiaries. Furthermore attention is paid to issues which generally arise when the European legislator attempts to introduce a new legal enterprise-form, such as the sup. The authors conclude that there are no irreconcilable differences between the laws of the eu-Member States that might hinder the introduction of the sup. Also the European principles of subsidiarity and proportionality will not constitute an obstacle.
Rousseau and Critical Theory
Authors: Ferrara Alessandro
Published: August 2017

InRousseau and Critical Theory, Alessandro Ferrara argues that among the modern philosophers who have shaped the world we inhabit, Rousseau is the one to whom we owe the idea that identity can be a source of normativity (moral and political) and that an identity’s potential for playing such a role rests on its capacity for being authentic. This normative idea of authenticity brings unity to Rousseau’s reflections on the negative effects of the social order, on the just political order, on education, and more generally, on ethics. It is also shown to contain important teachings for contemporary Critical Theory, contemporary views of self-constitution (Korsgaard, Frankfurt and Larmore), and contemporary political philosophy.
Synonymy of some Cicadellidae (Hemiptera: Auchenorrhyncha) known from Tuva Republic of Russia
Authors: EMELJANOV ALEXANDR F. , SARYGLAR SYLDYS H.
Published: August 2017

Five new species-level synonyms are established in the subfamily Deltocephalinae for the genera Achaetica Emeljanov, 1959, Mocuellus Ribaut, 1946, and Calamotettix Emeljanov, 1959. Chloriona jegoroviensis Vilbaste, 1980 is treated as a nomen nudum.