bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity Analysis of Vehicle Parameters for Heading Angle Control of an Unmanned Ground Vehicle
Authors: Sahoo Shubhashisa , Subramanian Shankar C. , Srivastava Suresh 
Published: July 2016

Even if there are many software and mathematical models available in the literature to analyze the dynamic performance of Unmanned Ground Vehicles (UGVs), it is always difficult to identify or collect the required vehicle parameters from the vehicle manufacturer for simulation. In analyzing the vehicle handling performance, a difficult and complex task is to use an appropriate tire model that can accurately characterize the ground-wheel interaction. Though, the well-known ‘Magic Formula’ is widely used for this purpose, it requires expensive test equipment to estimate the Magic Formula coefficients.
The design of longitudinal and lateral controllers plays a significant role in path tracking of an UGV. Though the speed of the vehicle may remain almost constant in most of the maneuvers such as lane change, Double Lane Change (DLC), step steer, cornering, etc., design of the lateral controller is always a challenging task as it depends on the vehicle parameters, road information and also on the steering actuator dynamics. Although a mathematical model is an abstraction of the actual system, the controller is designed based on this model and then deployed on the real system.
In this paper, a realistic mathematical model of the vehicle considering the steering actuator dynamics has been developed by calculating the cornering stiffnesses from the basic tire information and the vertical load on each tire. A heading angle controller of the UGV has been considered using the Point-to-Point navigation algorithm. Then, these controllers have been implemented on a test platform equipped with an Inertial Measurement Unit (IMU) and a Global Positioning System (GPS).
A wide range of experiments such as J-Turn, lane change and DLC have also been conducted for comparison with the simulation results. Sensitivity analysis has been carried out to check the robustness and stability of the controller by varying the cornering stiffness of tires, the most uncertain parameter. The longitudinal speed of the vehicle is assumed to vary between a minimum value of 1.4 m/s and a maximum value of 20 m/s. It has been found that when the vehicle is moving at a constant velocity of 3.2 m/s, a heading angle change of 20 degrees can be achieved within 3 seconds with 2% steady state error using a proportional controller. It was observed that at lower speeds, the controller is more sensitive to the steering actuator dynamics and at higher speeds, the controller is more sensitive to the cornering stiffness of tires.
Experimental Study for Propane Injection in Gasoline Engines
Authors: El-Sayed Mohamed E. M. , Byrley Don , Urbanik Wes , Selis Aaron , Kreft Jared , Li Tianao , Ng Kah Aik 
Published: July 2016

To study the effect of propane injection on gasoline fueled passenger vehicles fuel economy and cost saving the concept of a modular partial injection system was developed. The injection system was designed with the ability to be fitted in any gasoline fueled vehicle. The Control of the propane injection module was assembled with two stage system of regulators for coarse and fine adjustment of the propane flow to the engine. A digital manometer was used to adjust the pressure across the needle valve. The developed modular system was sealed and housed in a control box mounted to the side of the propane supply tank. The developed system was then fitted in a passenger vehicle and road tested for efficiency and cost savings.
In this paper, the design and development criteria in addition to the physical build of the modular propane injection system will be presented. Also, the fuel economy and cost saving from the road test results will be discussed.
Existence of Two Distinct Infectious Endogenous Retroviruses in Domestic Cats and Their Different Strategies for Adaptation to Transcriptional Regulation
Authors: Kuse Kyohei , Ito Jumpei , Miyake Ariko , Kawasaki Junna , Watanabe Shinya , Makundi Isaac , Ngo Minh Ha , Otoi Takeshige , Nishigaki Kazuo 
Published: July 2016

ABSTRACT
Endogenous retroviruses (ERVs) are the remnants of ancient retroviral infections of germ cells. Previous work identified one of the youngest feline ERV groups, ERV-DC, and reported that two ERV-DC loci, ERV-DC10 and ERV-DC18 (ERV-DC10/DC18), can replicate in cultured cells. Here, we identified another replication-competent provirus, ERV-DC14, on chromosome C1q32. ERV-DC14 differs from ERV-DC10/DC18 in its phylogeny, receptor usage, and, most notably, transcriptional activities; although ERV-DC14 can replicate in cultured cells, it cannot establish a persistent infection owing to its low transcriptional activity. Furthermore, we examined ERV-DC transcription and its regulation in feline tissues. Quantitative reverse transcription-PCR (RT-PCR) detected extremely low ERV-DC10 expression levels in feline tissues, and bisulfite sequencing showed that 5′ long terminal repeats (LTRs) of ERV-DC10/DC18 are significantly hypermethylated in feline blood cells. Reporter assays found that the 5′-LTR promoter activities of ERV-DC10/DC18 are high, whereas that of ERV-DC14 is low. This difference in promoter activity is due to a single substitution from A to T in the LTR, and reverse mutation at this nucleotide in ERV-DC14 enhanced its replication and enabled it to persistently infect cultured cells. Therefore, ERV-DC LTRs can be divided into two types based on this nucleotide, the A type or T type, which have strong or attenuated promoter activity, respectively. Notably, ERV-DCs with T-type LTRs, such as ERV-DC14, have expanded in the cat genome significantly more than A-type ERV-DCs, despite their low promoter activities. Our results provide insights into how the host controls potentially infectious ERVs and, conversely, how ERVs adapt to and invade the host genome.

IMPORTANCE
The domestic cat genome contains many endogenous retroviruses, including ERV-DCs. These ERV-DCs have been acquired through germ cell infections with exogenous retroviruses. Some of these ERV-DCs are still capable of producing infectious virions. Hosts must tightly control these ERVs because replication-competent viruses in the genome pose a risk to the host. Here, we investigated how ERV-DCs are adapted by their hosts. Replication-competent viruses with strong promoter activity, such as ERV-DC10 and ERV-DC18, were suppressed by promoter methylation in LTRs. On the other hand, replication-competent viruses with weak promoter activity, such as ERV-DC14, seemed to escape strict control via promoter methylation by the host. Interestingly, ERV-DCs with weak promoter activity, such as ERV-DC14, have expanded in the cat genome significantly more than ERV-DCs with strong promoter activity. Our results improve the understanding of the host-virus conflict and how ERVs adapt in their hosts over time.
Demethylation of the PD-1 Promoter Is Imprinted during the Effector Phase of CD8 T Cell Exhaustion
Authors: Ahn Eunseon , Youngblood Ben , Lee Junghwa , Lee Judong , Sarkar Surojit , Ahmed Rafi 
Published: July 2016

ABSTRACT
PD-1 is an inhibitory receptor that has a major role in T cell dysfunction during chronic infections and cancer. While demethylation of the PD-1 promoter DNA is observed in exhausted T cells isolated from chronically infected individuals, little is known about when this stable demethylation of PD-1 promoter DNA is programmed during the course of a chronic infection. To assess if PD-1 promoter DNA demethylation is impacted by prolonged stimulation during effector phase of chronic infection, we adoptively transferred virus-specific day 8 effector CD8 T cells from mice infected with lymphocytic choriomeningitis virus (LCMV) clone 13 into recipient mice that had cleared an acute infection. We observed that LCMV-specific CD8 T cells from chronically infected mice maintained their surface expression of PD-1 even after transfer into acute immune mice until day 45 posttransfer. Interestingly, the PD-1 transcriptional regulatory region continued to remain unmethylated in these donor CD8 T cells generated from a chronic infection. The observed maintenance of PD-1 surface expression and the demethylated PD-1 promoter were not a result of residual antigen in the recipient mice, because similar results were seen when chronic infection-induced effector cells were transferred into mice infected with a variant strain of LCMV (LCMV V35A) bearing a mutation in the cognate major histocompatibility complex class I (MHC-I) epitope that is recognized by the donor CD8 T cells. Importantly, the maintenance of PD-1 promoter demethylation in memory CD8 T cells was coupled with impaired clonal expansion and higher PD-1 re-expression upon secondary challenge. These data show that the imprinting of the epigenetic program of the inhibitory receptor PD-1 occurs during the effector phase of chronic viral infection.

IMPORTANCE
Since PD-1 is a major inhibitory receptor regulating T cell dysfunction during chronic viral infection and cancers, a better understanding of the mechanisms that regulate PD-1 expression is important. In this work, we demonstrate that the PD-1 epigenetic program in antigen-specific CD8 T cells is fixed during the priming phase of chronic infection.
The Ubiquitin Ligase Itch and Ubiquitination Regulate BFRF1-Mediated Nuclear Envelope Modification for Epstein-Barr Virus Maturation
Authors: Lee Chung-Pei , Liu Guan-Ting , Kung Hsiu-Ni , Liu Po-Ting , Liao Yen-Tzu , Chow Lu-Ping , Chang Ling-Shih , Chang Yu-Hsin , Chang Chou-Wei , Shu Wen-Chi , Angers Annie , Farina Antonella , Lin Su-Fang , Tsai Ching-Hwa , Bouamr Fadila , Chen Mei-Ru 
Published: July 2016

ABSTRACT
The cellular endosomal sorting complex required for transport (ESCRT) was recently found to mediate important morphogenesis processes at the nuclear envelope (NE). We previously showed that the Epstein-Barr virus (EBV) BFRF1 protein recruits the ESCRT-associated protein Alix to modulate NE structure and promote EBV nuclear egress. Here, we uncover new cellular factors and mechanisms involved in this process. BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. BFRF1 is ubiquitinated, and elimination of possible ubiquitination by either lysine mutations or fusion of a deubiquitinase hampers NE-derived vesicle formation and virus maturation. While it interacts with multiple Nedd4-like ubiquitin ligases, BFRF1 preferentially binds Itch ligase. We show that Itch associates with Alix and BFRF1 and is required for BFRF1-induced NE vesicle formation. Our data demonstrate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE and EBV maturation, uncovering novel regulatory mechanisms of nuclear egress of viral nucleocapsids.

IMPORTANCE
The nuclear envelope (NE) of eukaryotic cells not only serves as a transverse scaffold for cellular processes, but also as a natural barrier for most DNA viruses that assemble their nucleocapsids in the nucleus. Previously, we showed that the cellular endosomal sorting complex required for transport (ESCRT) machinery is required for the nuclear egress of EBV. Here, we further report the molecular interplay among viral BFRF1, the ESCRT adaptor Alix, and the ubiquitin ligase Itch. We found that BFRF1-induced NE vesicles are similar to those observed following EBV reactivation. The lysine residues and the ubiquitination of BFRF1 regulate the formation of BFRF1-induced NE-derived vesicles and EBV maturation. During the process, a ubiquitin ligase, Itch, preferably associates with BFRF1 and is required for BFRF1-induced NE vesicle formation. Therefore, our data indicate that Itch, ubiquitin, and Alix control the BFRF1-mediated modulation of the NE, suggesting novel regulatory mechanisms for ESCRT-mediated NE modulation.
Kinetics of HIV-1 Latency Reversal Quantified on the Single-Cell Level Using a Novel Flow-Based Technique
Authors: Martrus G. , Niehrs A. , Cornelis R. , Rechtien A. , García-Beltran W. , Lütgehetmann M. , Hoffmann C. , Altfeld M. 
Published: July 2016

ABSTRACT

HIV-1 establishes a pool of latently infected cells early following infection. New therapeutic approaches aiming at diminishing this persisting reservoir by reactivation of latently infected cells are currently being developed and tested. However, the reactivation kinetics of viral mRNA and viral protein production, and their respective consequences for phenotypical changes in infected cells that might enable immune recognition, remain poorly understood. We adapted a novel approach to assess the dynamics of HIV-1 mRNA and protein expression in latently and newly infected cells on the single-cell level by flow cytometry. This technique allowed the simultaneous detection of
gagpol
mRNA, intracellular p24 Gag protein, and cell surface markers. Following stimulation of latently HIV-1-infected J89 cells with human tumor necrosis factor alpha (hTNF-α)/romidepsin (RMD) or HIV-1 infection of primary CD4
+
T cells, four cell populations were detected according to their expression levels of viral mRNA and protein.
gagpol
mRNA in J89 cells was quantifiable for the first time 3 h after stimulation with hTNF-α and 12 h after stimulation with RMD, while p24 Gag protein was detected for the first time after 18 h poststimulation. HIV-1-infected primary CD4
+
T cells downregulated CD4, BST-2, and HLA class I expression at early stages of infection, proceeding Gag protein detection. In conclusion, here we describe a novel approach allowing quantification of the kinetics of HIV-1 mRNA and protein synthesis on the single-cell level and phenotypic characterization of HIV-1-infected cells at different stages of the viral life cycle.

IMPORTANCE
Early after infection, HIV-1 establishes a pool of latently infected cells, which hide from the immune system. Latency reversal and immune-mediated elimination of these latently infected cells are some of the goals of current HIV-1 cure approaches; however, little is known about the HIV-1 reactivation kinetics following stimulation with latency-reversing agents. Here we describe a novel approach allowing for the first time quantification of the kinetics of HIV-1 mRNA and protein synthesis after latency reactivation or
de novo
infection on the single-cell level using flow cytometry. This new technique furthermore enabled the phenotypic characterization of latently infected and
de novo
-infected cells dependent on the presence of viral RNA or protein.
JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships
Authors: Zeke András , Misheva Mariya , Reményi Attila , Bogoyevitch Marie A. 
Published: July 2016

SUMMARY
The c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states.
Characteristics of patients with type 2 diabetes mellitus newly treated with GLP-1 receptor agonists (CHADIG Study): a cross-sectional multicentre study in Spain
Authors: Conget Ignacio , Mauricio Dídac , Ortega Rafael , Detournay Bruno 
Published: July 2016

ObjectiveSeveral glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1Ra) have been made recently available in Spain for type 2 diabetes mellitus (DM2) treatment. There are no published data on the clinical and sociodemographic profile of patients initiating treatment with GLP-1Ra in Spain. Our objective was to understand these patients' characteristics in a real-world clinical practice setting.DesignCross-sectional observational study.SettingSpanish specialist outpatient clinics.Participants403 adults with DM2 initiating GLP-1Ra treatment were included.Primary and secondary outcome measuresSociodemographic and DM2-related clinical data, including treatment at and after GLP-1Ra initiation and comorbidities, were collected.ResultsEvaluable patients (n=403; 50.9% female) were included (July 2013 to March 2014) at 24 centres by 53 specialists (47 endocrinology, 6 internal medicine), with the following profile (value±SD): age (58.3±10.4 years), diabetes duration (9.9±7 years), body mass index (BMI; 36.2±5.5) and glycated haemoglobin (HbA1c; 8.4±1.4%); 14% had HbA1c≤7%. Previous antidiabetic treatment: 53.8% only oral antidiabetic drugs (OADs), 5.2% insulin and 40% insulin and OAD; of those receiving OAD, 35% single drug, 38.2% 2 drugs and 24% 3 drugs. Concomitant to GLP-1Ra, 55.3% were only on OAD, 36.2% on insulin and OAD, and 7.2% only on insulin. Of those receiving OAD, the GLP-1Ra was mainly associated with 1 drug (65%) or 2 drugs (31.8%). GLP-1Ra are frequently added to existing antidiabetic drugs, with dipeptidyl peptidase-4 inhibitors being the OAD most frequently switched (45% receiving 1 before starting GLP-1Ra, only 2.7% receiving it concomitantly).ConclusionsIn Spain, GLP-1Ra therapy is usually started in combination with OADs or OADs and insulin. These drugs are used in relatively young patients often not reaching therapeutic goals with other treatment combinations, roughly a decade after diagnosis and with a relatively high BMI. The latter could be explained by Spanish regional payers limiting reimbursed prescription to patients with a minimum BMI threshold (>30 in most regions, >35 in some).
Validation of the Singapore nomogram for outcome prediction in breast phyllodes tumours: an Australian cohort
Authors: Chng Tze Wei , Lee Jonathan Y H , Lee C Soon , Li HuiHua , Tan Min-Han , Tan Puay Hoon 
Published: July 2016

AimTo validate the utility of the Singapore nomogram for outcome prediction in breast phyllodes tumours.MethodsHistological parameters, surgical margin status and clinical follow-up data of 34 women diagnosed with phyllodes tumours were analysed. Biostatistics modelling was performed, and the concordance between predicted and observed survivals was calculated.ResultsWomen with a high nomogram score had an increased risk of developing relapse, which was predicted using the parameters defined by the Singapore nomogram.ConclusionsThe Singapore nomogram is useful in predicting outcome in breast phyllodes tumours when applied to an Australian cohort of 34 women.
Finite-size scaling law in single-crystalline Fe3O4 hollow nanostructures
Authors: Zhang Xiaoping , Wang Jun , Gao Miao 
Published: July 2016

Single-crystalline Fe3O4 hollow nanostructures (nanoring and nanotube) have been successfully synthesized by a hydrothermal method along with a heat treatment process. The temperature dependences of the magnetization of the hollow nanostructures were measured under a high vacuum ([Formula: see text] Torr) from 300[Formula: see text]K to 900[Formula: see text]K. The Curie temperatures of the nanoring and nanotube samples were found to decrease with decreasing the mean wall thickness. The Curie temperatures of the hollow magnetite nanostructures follow a finite-size scaling relation with the scaling exponent [Formula: see text]. By comparison with those of the zero-dimensional Fe3O4 particles and two-dimensional Fe3O4 films, we show that the scaling relation for our hollow nanostructures is in better agreement with the quasi-two-dimensional finite-size scaling law.
Critical Role of Coaptive Strain in Aortic Valve Leaflet Homeostasis: Use of a Novel Flow Culture Bioreactor to Explore Heart Valve Mechanobiology
Authors: Maeda Katsuhide , Ma Xiaoyuan , Chalajour Fariba , Hanley Frank L. , Riemer R. Kirk 
Published: July 2016

Background

Aortic valve (
AV
) disease presents critical situations requiring surgery in over 2% of the
US
population and is increasingly the reason for cardiac surgery. Throughout the
AV
cycle, mechanical forces of multiple types and varying intensities are exerted on valve leaflets. The mechanisms whereby forces regulate leaflet homeostasis are incompletely understood. We used a novel flow bioreactor culture to investigate alteration of
AV
opening or closure on leaflet genes.

Methods and Results

Culture of rat
AV
was conducted in a flow bioreactor for 7 days at 37°C under conditions approximating the normal stroke volume. Three force condition groups were compared: Cycling (n=8); always open (Open; n=3); or always closed (Closed; n=5). From each culture,
AV
leaflets were pooled by force condition and
RNA
expression evaluated using microarrays. Hierarchical clustering of 16 transcriptome data sets from the 3 groups revealed only 2 patterns of gene expression: Cycling and Closed groups clustered together, whereas Open
AV
were different (
P
<0.05). Sustained
AV
opening induced marked changes in expression (202 transcripts >2‐fold;
P
<0.05), whereas Closed
AV
exhibited similar expression pattern as Cycling (no transcripts >2‐fold;
P
<0.05). Comparison with human sclerotic and calcific
AV
transcriptomes demonstrated high concordance of >40 Open group genes with progression toward disease.

Conclusions

Failure of
AV
to close initiates an extensive response characterized by expression changes common to progression to calcific aortic valve disease.
AV
coaptation, whether phasic or chronic, preserved phenotypic gene expression. These results demonstrate, for the first time, that coaptation of valve leaflets is a fundamentally important biomechanical cue driving homeostasis.