bluuebunny/crossref_metadata_2025 huggingface dataset:
Domain Interaction Studies of Herpes Simplex Virus 1 Tegument Protein UL16 Reveal Its Interaction with Mitochondria
Authors: Chadha Pooja , Sarfo Akua , Zhang Dan , Abraham Thomas , Carmichael Jillian , Han Jun , Wills John W.
Published: November 2016

The UL16 tegument protein of herpes simplex virus 1 (HSV-1) is conserved among all herpesviruses and plays many roles during replication. This protein has an N-terminal domain (NTD) that has been shown to bind to several viral proteins, including UL11, VP22, and glycoprotein E, and these interactions are negatively regulated by a C-terminal domain (CTD). Thus, in pairwise transfections, UL16 binding is enabled only when the CTD is absent or altered. Based on these results, we hypothesized that direct interactions occur between the NTD and the CTD. Here we report that the separated and coexpressed functional domains of UL16 are mutually responsive to each other in transfected cells and form complexes that are stable enough to be captured in coimmunoprecipitation assays. Moreover, we found that the CTD can associate with itself. To our surprise, the CTD was also found to contain a novel and intrinsic ability to localize to specific spots on mitochondria in transfected cells. Subsequent analyses of HSV-infected cells by immunogold electron microscopy and live-cell confocal imaging revealed a population of UL16 that does not merely accumulate on mitochondria but in fact makes dynamic contacts with these organelles in a time-dependent manner. These findings suggest that the domain interactions of UL16 serve to regulate not just the interaction of this tegument protein with its viral binding partners but also its interactions with mitochondria. The purpose of this novel interaction remains to be determined.

IMPORTANCE
The HSV-1-encoded tegument protein UL16 is involved in multiple events of the virus replication cycle, ranging from virus assembly to cell-cell spread of the virus, and hence it can serve as an important drug target. Unfortunately, a lack of both structural and functional information limits our understanding of this protein. The discovery of domain interactions within UL16 and the novel ability of UL16 to interact with mitochondria in HSV-infected cells lays a foundational framework for future investigations aimed at deciphering the structure and function of not just UL16 of HSV-1 but also its homologs in other herpesviruses.
Myeloid Cell Turnover and Clearance
Authors: Janssen William J. , Bratton Donna L. , Jakubzick Claudia V. , Henson Peter M.
Published: November 2016

Given the dual and intrinsically contradictory roles of myeloid cells in both protective and yet also damaging effects of inflammatory and immunological processes, we suggest that it is important to consider the mechanisms and circumstances by which these cells are removed, either in the normal unchallenged state or during inflammation or disease. In this essay we address these subjects from a conceptual perspective, focusing as examples on four main myeloid cell types (neutrophils, monocytes, macrophages, and myeloid dendritic cells) and their clearance from the circulation or from naive and inflamed tissues. While the primary clearance process appears to involve endocytic uptake into macrophages, various tissue cell types can also recognize and remove dying cells, though their overall quantitative contribution is unclear. In fact, surprisingly, given the wealth of study in this area over the last 30 years, our conclusion is that we are still challenged with a substantial lack of mechanistic and regulatory understanding of when, how, and by what mechanisms migratory myeloid cells come to die and are recognized as needing to be removed, and indeed the precise processes of uptake of either the intact or fragmented cells. This reflects the extreme complexity and inherent redundancy of the clearance processes and argues for substantial investigative effort in this arena. In addition, it leads us to a sense that approaches to significant therapeutic modulation of selective myeloid clearance are still a long way off.
Ocular Tuberculosis
Authors: Albert Daniel M. , Raven Meisha L.
Published: November 2016

Ocular tuberculosis is an extrapulmonary mycobacterial infection with variable manifestations. The reported incidence of ocular involvement varies considerably, depending on the criteria used for diagnosis and the population sampled. However, tuberculosis is thought to affect the lungs in 80% of patients, with the remaining 20% being affected in other organs, such as the eye. It is imperative for physicians to consider this diagnosis in their differential, as ocular tuberculosis can present in a fashion similar to that of more common conditions causing ocular inflammation. In addition, prompt recognition of the clinical signs and symptoms leads to quicker initiation of antituberculosis therapy.
Interspecies Interactions between Clostridium difficile and Candida albicans
Authors: van Leeuwen Pim T. , van der Peet Jasper M. , Bikker Floris J. , Hoogenkamp Michel A. , Oliveira Paiva Ana M. , Kostidis Sarantos , Mayboroda Oleg A. , Smits Wiep Klaas , Krom Bastiaan P.
Published: November 2016

Candida albicans
and
Clostridium difficile
are two opportunistic pathogens that reside in the human gut. A few studies have focused on the prevalence of
C. albicans
in
C. difficile
-infected patients, but none have shown the interaction(s) that these two organisms may or may not have with each other. In this study, we used a wide range of different techniques to better understand this interaction at a macroscopic and microscopic level. We found that in the presence of
C. albicans
,
C. difficile
can survive under ambient aerobic conditions, which would otherwise be toxic. We also found that
C. difficile
affects the hypha formation of
C. albicans
, most likely through the excretion of
p
-cresol. This ultimately leads to an inability of
C. albicans
to form a biofilm. Our study provides new insights into interactions between
C. albicans
and
C. difficile
and bears relevance to both fungal and bacterial disease.
Long shadow of fear in an epidemic: fearonomic effects of Ebola on the private sector in Nigeria
Authors: Bali Sulzhan , Stewart Kearsley A , Pate Muhammad Ali
Published: November 2016

Background

The already significant impact of the Ebola epidemic on Guinea, Liberia and Sierra Leone, was worsened by a fear of contagion that aggravated the health crisis. However, in contrast to other Ebola-affected countries, Nigeria fared significantly better due to its swift containment of the disease. The objective of our study was to describe the impact of Ebola on the Nigerian private sector. This paper introduces and defines the termfearonomic effectas the direct and indirect economic effects of both misinformation as well as fear-induced aversion behaviour, exhibited by individuals, organisations or countries during an outbreak or an epidemic.

Methods

This study was designed as a cross-sectional mixed-methods study that used semistructured in-depth interviews and a supporting survey to capture the impact of Ebola on the Nigerian private sector after the outbreak. Themes were generated from the interviews on the direct and indirect impact of Ebola on the private sector; the impact of misinformation and fear-based aversion behaviour in the private sector.

Results

Our findings reveal that the fearonomic effects of Ebola included health service outages and reduced healthcare usage as a result of misinformation and aversion behaviour by both patients and providers. Although certain sectors (eg, health sector, aviation sector, hospitality sector) in Nigeria were affected more than others, no business was immune to Ebola's fearonomic effects. We describe how sectors expected to prosper during the outbreak (eg, pharmaceuticals), actually suffered due to the changes in consumption patterns and demand shocks.

Conclusion

In a high-stressor epidemic-like setting, altered consumption behaviour due to distorted disease perception, misinformation and fear can trigger short-term economic cascades that can disproportionately affect businesses and lead to financial insecurity of the poorest and the most vulnerable in a society.
The role of intersection and street design on severity of bicycle-motor vehicle crashes
Authors: Asgarzadeh Morteza , Verma Santosh , Mekary Rania A , Courtney Theodore K , Christiani David C
Published: November 2016

Background

Safety concerns are a major barrier to cycling. Intersection and street design variables such as intersection angles and street width might contribute to the severity of crashes and the safety concerns. In this study we examined whether these design variables were associated with bicycle-motor vehicle crashes (BMVC) severity.

Methods

Using the geographical information system and latitudes/longitudes recorded by the police using a global positioning device, we extracted intersection angles, street width, bicycle facilities, posted speed limits and annual average daily traffic from 3266 BMVC data from New York City police records. Additional variables about BMVC, including age and sex of the bicyclist, time of the day, road surface conditions, road character, vehicle type and injury severity, were obtained from police reports. Injury severity was classified as severe (incapacitating or killed) or non-severe (non-incapacitating, possible injury). The associations between injury severity and environment design variables were examined using multivariate log-binomial regression model.

Findings

Compared with crashes at orthogonal intersections, crashes at non-orthogonal intersections had 1.37 times (95% CI 1.05 to 1.80) and non-intersection street segments had 1.31 times (95% CI 1.01 to 1.70) higher risk of a severe injury. Crashes that involved a truck or a bus were twice as likely to result in a severe injury outcome; street width was not significantly associated with injury severity.

Conclusion

Crashes at non-orthogonal intersections and non-intersection segments are more likely to result in higher injury severity. The findings can be used to improve road design and develop effective safety interventions.
Planning, managing and equipping an intensive care unit within a veterinary facility
Authors: Smith Caroline , Witchell Holly
Published: November 2016

An intensive care unit (ICU) is a specially staffed and equipped, separate and self‐contained area of a hospital dedicated to the management and monitoring of patients with life‐threatening conditions. Patient demands require staff with special expertise and facilities for the support of vital functions. Careful thought is essential when creating an ICU facility, as each hospital will have its own individual needs and expectations for what should be offered. This article gives an overview of the main points to consider when planning, managing and equipping an ICU.
Being resilient: business continuity principles for veterinary practice
Authors: Hills Mils
Published: November 2016

No matter what the cause of disruption, businesses need to survive. Mils Hills discusses the key principles of business continuity and explains how these can be applied in veterinary practice.
CEPC partial double ring lattice design and SPPC lattice design
Authors: Su Feng , Gao Jie , Wang Dou , Wang Yiwei , Tang Jingyu , Bian Tianjian , Bai Sha , Geng Huiping , Zhang Yuan , Guo Yuanyuan , Peng Yuemei , Zou Ye , Chen Yukai , Xiao Ming
Published: November 2016

In this paper, we introduce the layout and lattice design of Circular-Electron-Positron-Collider (CEPC) partial double ring scheme and the lattice design of Super-Proton-Proton-Collider (SPPC). The baseline design of CEPC is a single beam-pipe electron positron collider, which has to adopt pretzel orbit scheme and it is not suitable to serve as a high luminosity [Formula: see text] factory. If we choose partial double ring scheme, we can get a higher luminosity with lower power and be suitable to serve as a high luminosity [Formula: see text] factory. In this paper, we discuss the details of CEPC partial double ring lattice design and show the dynamic aperture study and optimization. We also show the first version of SPPC lattice although it needs lots of work to do and to be optimized.
On the BRST and finite field-dependent BRST of a model where vector and axial vector interactions get mixed up with different weights
Authors: Yasmin Safia , Rahaman Anisur
Published: November 2016

The generalized version of a lower dimensional model where vector and axial vector interactions get mixed up with different weights is considered. The bosonized version of which does not possess the local gauge symmetry. An attempt has been made here to construct the BRST invariant reformulation of this model using Batalin–Fradlin and Vilkovisky formalism. It is found that the extra field needed to make it gauge invariant turns into Wess–Zumino scalar with appropriate choice of gauge fixing. An application of finite field-dependent BRST and anti-BRST transformation is also made here in order to show the transmutation between the BRST symmetric and the usual nonsymmetric version of the model.
Experimental investigation and numerical modeling of the hydration operation of date fruits
Authors: Lakoud Atef , Curet Sébastien , Hassouna Mnasser
Published: November 2016

Hydration represents the main unit operation in the industrial thermal process of dry dates. In this work, Tunisian Deglet Nour dates were hydrated experimentally at a laboratory scale by using saturated air as it is commonly undertaken in industry. This study focuses on the modeling of this unit operation in order to control the moisture uptake phenomenon during processing. A physic-based simplified numerical model describing moisture transfer during hydration was implemented in COMSOL[Formula: see text]Multiphysics software. The model considers the real geometry of dates instead of approaching the fruits by simplified shapes. Moisture diffusivities of two types of Deglet Nour dry dates characterized by different maturation stages were estimated. Results showed a good agreement between experimental and numerically computed values of average moisture content. Moisture profile in dates flesh was computed numerically using estimated moisture diffusivities. The numerical model proposed in this work could be therefore employed as a predictive tool to simulate and optimize the hydration operation of dates.
Nutrient Pollution: A Wicked Challenge for Economic Instruments
Authors: Shortle James , Horan Richard D.
Published: November 2016

Nutrient pollution is one of the most important problems facing aquatic systems globally. The problem qualifies as a wicked one, involving multiple pollutants from multiple sources interacting in complex ways over space and time along multiple pathways, with uncertainty present at each stage of the process—from pollutant generation to the final ecological and economic impacts. We draw on a diverse interdisciplinary literature to identify challenges for implementing efficient solutions using economic instruments, but also describe why economic research and concern for economic efficiency are of crucial importance to the selection of instruments to address the problem, and propose a general equilibrium economic geography paradigm for research on instrument design and choice.
Data-driven inverse dynamics for human motion
Authors: Lv Xiaolei , Chai Jinxiang , Xia Shihong
Published: November 2016

Inverse dynamics is an important and challenging problem in human motion modeling, synthesis and simulation, as well as in robotics and biomechanics. Previous solutions to inverse dynamics are often noisy and ambiguous particularly when double stances occur. In this paper, we present a novel inverse dynamics method that accurately reconstructs biomechanically valid contact information, including center of pressure, contact forces, torsional torques and internal joint torques from input kinematic human motion data. Our key idea is to apply statistical modeling techniques to a set of preprocessed human kinematic and dynamic motion data captured by a combination of an optical motion capture system, pressure insoles and force plates. We formulate the data-driven inverse dynamics problem in a maximum a posteriori (MAP) framework by estimating the most likely contact information and internal joint torques that are consistent with input kinematic motion data. We construct a low-dimensional data-driven prior model for contact information and internal joint torques to reduce ambiguity of inverse dynamics for human motion. We demonstrate the accuracy of our method on a wide variety of human movements including walking, jumping, running, turning and hopping and achieve state-of-the-art accuracy in our comparison against alternative methods. In addition, we discuss how to extend the data-driven inverse dynamics framework to motion editing, filtering and motion control.
Sex differences in the metabolic dysfunction and insulin resistance of skeletal muscle glucose transport following high fructose ingestion
Authors: Rattanavichit Yupaporn , Chukijrungroat Natsasi , Saengsirisuwan Vitoon
Published: November 2016

The role of high fructose ingestion (HFI) in the development of conditions mimicking human metabolic syndrome has mostly been demonstrated in male animals; however, the extent of HFI-induced metabolic alterations in females remains unclear. The present study investigated whether HFI-induced metabolic perturbations differ between sexes and whether HFI aggravates the metabolic disturbances under ovarian hormone deprivation. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were given either water or liquid fructose (10% wt/vol) for 6 wk. Blood pressure, glucose tolerance, insulin-stimulated glucose transport activity and signaling proteins, including insulin receptor (IR), insulin receptor substrate 1 (IRS-1), Akt, Akt substrate of 160 kDa (AS160), AMPKα, JNK, p38 MAPK, angiotensin-converting enzyme (ACE), ANG II type 1 receptor (AT1R), ACE2, and Mas receptor (MasR) in skeletal muscle, were evaluated. We found that HFI led to glucose intolerance and hypertension in male and OVX rats but not in female rats with intact ovaries. Moreover, HFI did not induce insulin resistance in the skeletal muscle of female and OVX rats but impaired the insulin-stimulated glucose transport activity in the skeletal muscle of male rats, which was accompanied by lower insulin-stimulated IRS-1 Tyr989 (44%), Akt Ser473 (30%), and AS160 Ser588 (43%), and increases in insulin-stimulated IRS-1 Ser307 (78%), JNK Thr183/Tyr185 (69%), and p38 MAPK Thr180/Tyr182 (81%). The results from the present study show sex differences in the development of metabolic syndrome-like conditions and indicate the protective role of female sex hormones against HFI-induced cardiometabolic abnormalities.
Mesenteric vascular dysregulation and intestinal inflammation accompanies experimental spinal cord injury
Authors: Besecker Emily M. , Deiter Gina M. , Pironi Nicole , Cooper Timothy K. , Holmes Gregory M.
Published: November 2016

Cervical and high thoracic spinal cord injury (SCI) drastically impairs autonomic nervous system function. Individuals with SCI at thoracic spinal level 5 (T5) or higher often present cardiovascular disorders that include resting systemic arterial hypotension. Gastrointestinal (GI) tissues are critically dependent upon adequate blood flow and even brief periods of visceral hypoxia triggers GI dysmotility. The aim of this study was to test the hypothesis that T3-SCI induces visceral hypoperfusion, diminished postprandial vascular reflexes, and concomitant visceral inflammation. We measured in vivo systemic arterial blood pressure and superior mesenteric artery (SMA) and duodenal blood flow in anesthetized T3-SCI rats at 3 days and 3 wk postinjury either fasted or following enteral feeding of a liquid mixed-nutrient meal (Ensure). In separate cohorts of fasted T3-SCI rats, markers of intestinal inflammation were assayed by qRT-PCR. Our results show that T3-SCI rats displayed significantly reduced SMA blood flow under all experimental conditions ( P < 0.05). Specifically, the anticipated elevation of SMA blood flow in response to duodenal nutrient infusion (postprandial hyperemia) was either delayed or absent after T3-SCI. The dysregulated SMA blood flow in acutely injured T3-SCI rats coincides with abnormal intestinal morphology and elevation of inflammatory markers, all of which resolve after 3 wk. Specifically, Icam1, Ccl2 (MCP-1), and Ccl3 (MIP-1α) were acutely elevated following T3-SCI. Our data suggest that arterial hypotension diminishes mesenteric blood flow necessary to meet mucosal demands at rest and during digestion. The resulting GI ischemia and low-grade inflammation may be an underlying pathology leading to GI dysfunction seen following acute T3-SCI.
Cocaine sensitization increases subthreshold activity in dopamine neurons from the ventral tegmental area
Authors: Arencibia-Albite Francisco , Vázquez-Torres Rafael , Jiménez-Rivera Carlos A.
Published: November 2016

The progressive escalation of psychomotor responses that results from repeated cocaine administration is termed sensitization. This phenomenon alters the intrinsic properties of dopamine (DA) neurons from the ventral tegmental area (VTA), leading to enhanced dopaminergic transmission in the mesocorticolimbic network. The mechanisms underlying this augmented excitation are nonetheless poorly understood. DA neurons display the hyperpolarization-activated, nonselective cation current, dubbed Ih. We recently demonstrated that Ih and membrane capacitance are substantially reduced in VTA DA cells from cocaine-sensitized rats. The present study shows that 7 days of cocaine withdrawal did not normalize Ih and capacitance. In cells from cocaine-sensitized animals, the amplitude of excitatory synaptic potentials, at −70 mV, was ∼39% larger in contrast to controls. Raise and decay phases of the synaptic signal were faster under cocaine, a result associated with a reduced membrane time constant. Synaptic summation was paradoxically elevated by cocaine exposure, as it consisted of a significantly reduced summation indexed but a considerably increased depolarization. These effects are at least a consequence of the reduced capacitance. Ih attenuation is unlikely to explain such observations, since at −70 mV, no statistical differences exist in Ih or input resistance. The neuronal shrinkage associated with a diminished capacitance may help to understand two fundamental elements of drug addiction: incentive sensitization and negative emotional states. A reduced cell size may lead to substantial enhancement of cue-triggered bursting, which underlies drug craving and reward anticipation, whereas it could also result in DA depletion, as smaller neurons might express low levels of tyrosine hydroxylase.

NEW & NOTEWORTHY This work uses a new approach that directly extracts important biophysical parameters from alpha function-evoked synaptic potentials. Two of these parameters are the cell membrane capacitance (Cm) and rate at any time point of the synaptic waveform. The use of such methodology shows that cocaine sensitization reduces Cm and increases the speed of synaptic signaling. Paradoxically, although synaptic potentials show a faster decay under cocaine their temporal summation is substantially elevated.
Context-dependent plasticity in the subcortical encoding of linguistic pitch patterns
Authors: Lau Joseph C. Y. , Wong Patrick C. M. , Chandrasekaran Bharath
Published: November 2016

We examined the mechanics of online experience-dependent auditory plasticity by assessing the influence of prior context on the frequency-following responses (FFRs), which reflect phase-locked responses from neural ensembles within the subcortical auditory system. FFRs were elicited to a Cantonese falling lexical pitch pattern from 24 native speakers of Cantonese in a variable context, wherein the falling pitch pattern randomly occurred in the context of two other linguistic pitch patterns; in a patterned context, wherein, the falling pitch pattern was presented in a predictable sequence along with two other pitch patterns, and in a repetitive context, wherein the falling pitch pattern was presented with 100% probability. We found that neural tracking of the stimulus pitch contour was most faithful and accurate when listening context was patterned and least faithful when the listening context was variable. The patterned context elicited more robust pitch tracking relative to the repetitive context, suggesting that context-dependent plasticity is most robust when the context is predictable but not repetitive. Our study demonstrates a robust influence of prior listening context that works to enhance online neural encoding of linguistic pitch patterns. We interpret these results as indicative of an interplay between contextual processes that are responsive to predictability as well as novelty in the presentation context.

NEW & NOTEWORTHY Human auditory perception in dynamic listening environments requires fine-tuning of sensory signal based on behaviorally relevant regularities in listening context, i.e., online experience-dependent plasticity. Our finding suggests what partly underlie online experience-dependent plasticity are interplaying contextual processes in the subcortical auditory system that are responsive to predictability as well as novelty in listening context. These findings add to the literature that looks to establish the neurophysiological bases of auditory system plasticity, a central issue in auditory neuroscience.
High Dose, Prolonged Epsilon Aminocaproic Acid Infusion, and Recombinant Factor VII for Massive Postoperative Retroperitoneal Hemorrhage following Splenectomy
Authors: Lee Alex T. , Barnes Christopher R. , Jain Shweta , Pauldine Ronald
Published: November 2016

The antifibrinolytic agentε-aminocaproic acid is used to decrease procedural blood loss in a variety of high risk surgeries. The utility of recombinant factor VII administration in massive hemorrhage has also been reported in a variety of settings, though the impact in a surgical context remains unclear. We describe the case of a patient who underwent massive open splenectomy and developed diffuse retroperitoneal bleeding on postoperative day one. Massive transfusion was initiated, but attempts to control hemorrhage with surgical and interventional radiology approaches were unsuccessful, as was recombinant factor VII administration. Commencement of a high dose aminocaproic acid infusion was followed by a prominent rise in fibrinogen levels and stabilization of the hemorrhage. Indications, dosages, and adverse effects ofε-aminocaproic acid as described in the literature are reviewed.
A General Range-Velocity Processing Scheme for Discontinuous Spectrum FMCW Signal in HFSWR Applications
Authors: Pan Mengguan , Chen Baixiao , Yang Minglei
Published: November 2016

Discontinuous spectrum signal which has separate subbands distributed over a wide spectrum band is a solution to synthesize a wideband waveform in a highly congested spectrum environment. In this paper, we present a general range-velocity processing scheme for the discontinuous spectrum-frequency modulated continuous wave (DS-FMCW) signal specifically. In range domain, we propose a simple time rearrangement operation which converts the range transform problem of the DS-FMCW signal to a general spectral estimation problem of nonuniformly sampled data. Conventional periodogram results in a dirty range spectrum with high sidelobes which cannot be suppressed by traditional spectral weighting. In this paper, we introduce the iterative adaptive approach (IAA) in the estimation of the range spectrum. IAA is shown to have the ability to provide a clean range spectrum. On the other hand, the discontinuity of the signal spectrum has little impact on the velocity processing. However, with the range resolution improved, the influence of the target motion becomes nonnegligible. We present a velocity compensation strategy which includes the intersweep compensation and in-sweep compensation. Our processing scheme with the velocity compensation is shown to provide an accurate and clean range-velocity image which benefits the following detection process.
A High Performance Target Tracing Transmission Model Oriented to Lifecycle Maximization
Authors: Zhao Zhong-Nan , Qiao Pei-Li , Wang Jian
Published: November 2016

For the high speed sensor networks applications such as Internet of Things, multimedia transmission, the realization of high-rate transmission under limited resources has become a problem to be solved. A high speed transmission and energy optimization model oriented to lifecycle maximization is proposed in this paper. Based on information-directed mechanism, the energy threshold set and the relay node distance selection will be done in the process of target tracing, as a result, retaining a balance between transmission rate and energy consumption. Meanwhile, multiagent coevolution is adopted to achieve the maximum of network lifecycle. Comparing with the relevant methods, indexes for network such as hops, throughput, and number of active nodes, standard deviation of remaining energy, and the network lifecycle are considered, and the simulated experiments show that the proposed method will promote the transmission rate effectively, prolong the network lifecycle, and improve network performance as a whole.
Effectiveness of Moderate Intensity Interval Training as an Index of Autonomic Nervous Activity
Authors: Kai Satoru , Nagino Koji , Ito Takayoshi , Oi Rie , Nishimura Kazushi , Morita Shuhei , Yaoi Riyo
Published: November 2016

The purpose of this study was to examine the effects of moderate intensity interval training from the change of the autonomic nervous activity. Ten male volunteers aged 21-22 years were studied. After 10-minute rest in a seated position, the subjects were asked to perform the strength of moderate cycling exercise in ergometer. Cycling rate was done in 50 times/min. Load resistance of the ergometer was set to 2.0 kgm. Subjects paused the exercise when the heart rate becomes 120 beats/min. Subjects have resumed the exercise when the heart rate returns to the value at rest. This trial was repeated twice. The experiment was ended when the heart rate of the subjects has returned to resting level. When the heart rate during exercise is maintained to less than 120 beats/min, sympathetic nerve activity during exercise did not work actively compared to the baseline. Vagus nerve activity after exercise cessation exceeds the baseline. It is clarified that the exercise as well as activating the vagus nerve activity stimulates the total autonomic nervous activity. It has revealed that at the time of interval training at moderate load the vagus nerve activity can be carried out.
Nephroblastoma Arising from Primary Testicular Germ Cell Tumor: A Case Report and Literature Review
Authors: Alatassi Houda , O’Bryan Brittany E. , Messer Jamie C. , Wang Zhenglong
Published: November 2016

Adult extrarenal nephroblastoma is a very rare tumor. Nephroblastoma arising from primary testicular germ cell tumor is exceedingly rare. To our knowledge, only three cases have been reported in the English literature. We report a case of a 19-year-old man who presented with a large right testicle. Image studies showed a large retroperitoneal mass along with liver and lung metastases. Orchiectomy demonstrated a mixed germ cell tumor composed of yolk sac tumor, embryonal carcinoma, and mature and immature teratoma with a significant portion of nephroblastoma. The patient received chemotherapy and no recurrence was noted during six months of followup. WT-1 expression was also studied due to the lack of consistency of its expression in testicular nephroblastoma in the literature. We also present a discussion and review of the literature due to its rarity, which indicate an adverse prognosis for patients with nephroblastoma components receiving standard chemotherapeutical regimes for testicular germ cell tumors.
Flutter Characteristic Study of Composite Sandwich Panel with Functionally Graded Foam Core
Authors: Jin Peng , Zhong Xiaoping
Published: November 2016

This paper attempts to investigate the flutter characteristic of sandwich panel composed of laminated facesheets and a functionally graded foam core. The macroscopic properties of the foam core change continuously along this direction parallel to the facesheet lamina. The model used in the study is a simple sandwich panel-wing clamped at the root, with three simple types of grading strategies for FGM core: (1) linear grading strategy in the chord-wise direction, (2) linear grading strategy in the span-wise direction, and (3) bilinear grading of properties of foam core across the panel. The results show that use of FGM core has the potential to increase the flutter speed of the sandwich panel. Finally, a minimum weight design of composite sandwich panel with lamination parameters of facesheet and density distribution of foam core as design variables is conducted using particle swarm optimization (PSO).
Mathematical Modeling of Hidden Intimate Partner Violence in Spain: A Quantitative and Qualitative Approach
Authors: Poza E. De la , Jódar L. , Barreda S.
Published: November 2016

The fact that women are abused by their male partner is something that happens worldwide in the 21st century. In numerous cases, abuse only becomes publicly known when a fatal event occurs and is beyond any possible remedy, that is, when men murder their female partner. Since 2003, 793 (September 4, 2015) women have been assassinated by their significant other or excouple in Spain. Only 7.2% of murdered women had reported their fear and previous intimate partner violence (IPV) to the police. Even when the number of female victims is comparable to the number of victims by terrorism, the Government has not assigned an equal amount of resources to diminish the magnitude of this hidden social problem. In this paper, a mathematical epidemiological model to forecast intimate partner violence in Spain is constructed. Both psychological and physical aggressor subpopulations are predicted and simulated. The model’s robustness versus uncertain parameters is studied by a sensitivity analysis.
A H-Infinity Control for Path Tracking with Fuzzy Hyperbolic Tangent Model
Authors: Shi Guangsi , Yang Jue , Zhao Xuan , Li Yanfeng , Zhao Yalun , Li Jian
Published: November 2016

To achieve the goal of driver-less underground mining truck, a fuzzy hyperbolic tangent model is established for path tracking on an underground articulated mining truck. Firstly, the sample data of parameters are collected by the driver controlling articulated vehicle at a speed of 3 m/s, including both the lateral position deviation and the variation of heading angle deviation. Then, according to the improved adaptive BP neural network model and deriving formula of mediation rate of error estimator by the method of Cauchy robust, the weights are identified. Finally, H-infinity control controller is designed to control steering angle. The results of hardware-in-the-loop simulation show that lateral position deviation, heading angle deviation, and steering angle of the vehicle can be controlled, respectively, at 0.024 m, 0.08 rad, and 0.21 rad. All the deviations are asymptotically stable, and error control is in less than 2%. The method is demonstrated to be effective and reliable in path tracking for the underground vehicles.
Urinary Melatonin in Relation to Postmenopausal Breast Cancer Risk According to Melatonin 1 Receptor Status
Authors: Devore Elizabeth E. , Warner Erica T. , Eliassen A. Heather , Brown Susan B. , Beck Andrew H. , Hankinson Susan E. , Schernhammer Eva S.
Published: November 2016

Background: Urinary melatonin levels have been associated with a reduced risk of breast cancer in postmenopausal women, but this association might vary according to tumor melatonin 1 receptor (MT1R) expression.

Methods: We conducted a nested case–control study among 1,354 postmenopausal women in the Nurses' Health Study, who were cancer free when they provided first-morning spot urine samples in 2000 to 2002; urine samples were assayed for 6-sulfatoxymelatonin (aMT6s, a major metabolite of melatonin). Five-hundred fifty-five of these women developed breast cancer before May 31, 2012, and were matched to 799 control subjects. In a subset of cases, immunohistochemistry was used to determine MT1R status of tumor tissue. We used multivariable-adjusted conditional logistic regression to estimate the relative risk (RR) of breast cancer [with 95% confidence intervals (CI)] across quartiles of creatinine-standardized urinary aMT6s level, including by MT1R subtype.

Results: Higher urinary melatonin levels were suggestively associated with a lower overall risk of breast cancer (multivariable-adjusted RR = 0.78; 95% CI = 0.61–0.99, comparing quartile 4 vs. quartile 1; Ptrend = 0.08); this association was similar for invasive vs. in situ tumors (Pheterogeneity = 0.12). There was no evidence that associations differed according to MT1R status of the tumor (e.g., Pheterogeneity for overall breast cancer = 0.88).

Conclusions: Higher urinary melatonin levels were associated with reduced breast cancer risk in this cohort of postmenopausal women, and the association was not modified by MT1R subtype.

Impact: Urinary melatonin levels appear to predict the risk of breast cancer in postmenopausal women. However, future research should evaluate these associations with longer-term follow-up and among premenopausal women. Cancer Epidemiol Biomarkers Prev; 26(3); 413–9. ©2016 AACR.
Tumor-Specific Uptake of Fluorescent Bevacizumab–IRDye800CW Microdosing in Patients with Primary Breast Cancer: A Phase I Feasibility Study
Authors: Lamberts Laetitia E. , Koch Maximillian , de Jong Johannes S. , Adams Arthur L.L. , Glatz Jürgen , Kranendonk Mariëtte E.G. , Terwisscha van Scheltinga Anton G.T. , Jansen Liesbeth , de Vries Jakob , Lub-de Hooge Marjolijn N. , Schröder Carolien P. , Jorritsma-Smit Annelies , Linssen Matthijs D. , de Boer Esther , van der Vegt Bert , Nagengast Wouter B. , Elias Sjoerd G. , Oliveira Sabrina , Witkamp Arjen J. , Mali Willem P.Th.M. , Van der Wall Elsken , van Diest Paul J. , de Vries Elisabeth G.E. , Ntziachristos Vasilis , van Dam Gooitzen M.
Published: November 2016

Purpose: To provide proof of principle of safety, breast tumor–specific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab–IRDye800CW targeting VEGF-A in patients with breast cancer.

Experimental Design: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab–IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue.

Results: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level.

Conclusions: Our study shows that systemic administration of the bevacizumab–IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor margin uptake as evaluated by a systematic validation methodology. The findings are a step toward a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue. Clin Cancer Res; 23(11); 2730–41. ©2016 AACR.
Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei
Authors: Dillon Magnus T. , Barker Holly E. , Pedersen Malin , Hafsi Hind , Bhide Shreerang A. , Newbold Kate L. , Nutting Christopher M. , McLaughlin Martin , Harrington Kevin J.
Published: November 2016

AZD6738 is an orally active ATR inhibitor (ATRi) currently in phase I clinical trials. We found in vitro growth inhibitory activity of this ATRi in a panel of human cancer cell lines. We demonstrated radiosensitization by AZD6738 to single radiation fractions in multiple cancer cell lines independent of both p53 and BRCA2 status by the clonogenic assay. Radiosensitization by AZD6738 to clinically relevant doses of fractionated radiation was demonstrated in vitro using a 3D tumor spheroid model and, in vivo, AZD6738 radiosensitized by abrogating the radiation-induced G2 cell-cycle checkpoint and inhibiting homologous recombination. Mitosis with damaged DNA resulted in mitotic catastrophe as measured by micronucleus formation by live-cell fluorescent-ubiquitination cell-cycle imaging of cell-cycle progression and nuclear morphology. Induction of micronuclei was significantly more prominent for AZD6738 compared with inhibition of the downstream kinase CHK1 alone at isoeffective doses. Micronuclei were characterized as acentric chromosomal fragments, which displayed characteristics of increased DNA damage and cell-cycle dyssynchrony when compared with the primary nucleus. Mol Cancer Ther; 16(1); 25–34. ©2016 AACR.
Targeting Inflammation in Cancer Prevention and Therapy
Authors: Todoric Jelena , Antonucci Laura , Karin Michael
Published: November 2016

Inflammation is associated with the development and malignant progression of most cancers. As most of the cell types involved in cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammation can result in immunosuppression, thereby providing a preferred background for tumor development. In clinical trials, lifestyle modifications including healthy diet, exercise, alcohol, and smoking cessation have proven effective in ameliorating inflammation and reducing the risk of cancer-related deaths. In addition, consumption of certain anti-inflammatory drugs, including aspirin, can significantly reduce cancer risk, suggesting that common nonsteroidal anti-inflammatory drugs (NSAID) and more specific COX2 inhibitors can be used in cancer prevention. In addition to being examined for their preventative potential, both NSAIDs and more potent anti-inflammatory antibody-based drugs need to be tested for their ability to augment the efficacy of more conventional therapeutic approaches on the basis of tumor resection, radiation, and cytotoxic chemicals. Cancer Prev Res; 9(12); 895–905. ©2016 AACR.
Inhibition of ERK1/2 Signaling Pathway is Involved in Melatonin's Antiproliferative Effect on Human MG-63 Osteosarcoma Cells
Authors: Liu Lifeng , Xu Ying , Reiter Russel J. , Pan Yutao , Chen Di , Liu Yangzhou , Pu Xingyu , Jiang Liguo , Li Zengchun
Published: November 2016

Background: In a previous study, we found that melatonin inhibits MG-63 osteosarcoma cell proliferation; however, the underlying mechanisms remain elusive. Mitogen-activated protein kinase (MAPK) and Akt signaling pathways play key roles in the anticancer effects of melatonin. Aims: The present study investigated whether MAPK and Akt signaling pathways are involved in melatonin's antiproliferative actions on the human MG-63 osteosarcoma cells. Methods/Results: Western blot analysis confirmed that melatonin significantly inhibited phosphorylation of ERK1/2 but not p38, JNK, or Akt. The expression of ERK1/2, p38, JNK, and Akt was not altered by melatonin. PD98059 and melatonin alone, and especially in combination, significantly inhibited cell proliferation. The changes included G1 and G2/M phase arrest of the cell cycle, and a downregulation of the expression at both the protein and mRNA levels of cyclin D1 and CDK4 (related to the G1 phase) and of cyclin B1 and CDK1 (related to the G2/M phase) as measured by flow cytometry after propidium iodide staining, and both western blot and real-time PCR, respectively. Furthermore, the combination of PD98059 and melatonin synergistically and markedly augmented the action of either agent alone. Co-immunoprecipitation further confirmed that there was an interaction between p-ERK1/2 and cyclin D1, CDK4, cyclin B1, or CDK1, which was blunted in the presence of melatonin or PD98059. Conclusion: These findings suggest that melatonin's antiproliferative action is mediated by inhibition of the ERK1/2 signaling pathway rather than the p38, JNK, or Akt pathways.
Cardiac Surgery for Carcinoid Heart Disease: A Weapon Not to Be Misused
Authors: Bonou Maria , Kapelios Chris J. , Kaltsas Gregory , Perreas Konstantinos , Toutouzas Konstantinos , Barbetseas John
Published: November 2016

Carcinoid heart disease (CHD) complicates approximately 25% of patients with a carcinoid tumor and carcinoid syndrome and leads to heart valve degeneration with mixed-stenotic and regurgitation pathology and consequent heart failure (HF) leading to significant morbidity and mortality. Cardiac surgery in symptomatic, severe CHD leads to significantly better functional capacity and prolonged survival when compared to medical treatment alone. Recent studies have shown improvement in postoperative outcomes of patients undergoing surgery for CHD over the last decades. The trend for early diagnosis and application of surgery prior to the manifestation of HF symptoms, which tended to develop during the previous years, does not seem justifiable based on the findings of recent studies. Therefore, the optimal timing of intervention in CHD and the type of valve that should preferably be used remain issues of controversy. This review comprehensively examines the existing literature on the treatment options for patients with CHD, with a special focus on short- and long-term survival after cardiac surgery, and discusses the selection of the exact patient profile and intervention timing that are more likely to optimize the benefit-to-risk ratio for surgical intervention.
Cytokines and Recurrence of Macular Edema after Intravitreal Ranibizumab in Patients with Branch Retinal Vein Occlusion
Authors: Noma Hidetaka , Mimura Tatsuya , Yasuda Kanako , Nakagawa Hayate , Motohashi Ryosuke , Kotake Osamu , Shimura Masahiko
Published: November 2016

The aqueous humor levels of cytokines and growth/inflammatory factors were measured in 46 branch retinal vein occlusion (BRVO) patients with macular edema (ME) who were treated with intravitreal ranibizumab injection (IRI). Patients with recurrence of ME received further IRI as needed. The number of IRIs was significantly correlated with age, baseline best-corrected visual acuity, and baseline central macular thickness (CMT), as well as the baseline aqueous levels of 5 cytokines/factors (soluble vascular endothelial growth factor receptor-1, platelet-derived growth factor-AA [PDGF-AA], soluble intercellular adhesion molecule-1, interleukin-6 [IL-6], and IL-8). Multivariate linear regression analysis with stepwise selection confirmed that age, baseline CMT, and baseline PDGF-AA level were independent determinants of the number of IRIs. These findings suggest that inflammatory factors may influence the recurrence of ME in BRVO patients, and that PDGF-AA might be a useful indicator of the number of IRIs required to control ME.