bluuebunny/crossref_metadata_2025_split huggingface dataset:
POINT-TO-POINT (PTP) CONTROL PERFORMANCES OF AN UPPER LIMB ROBOTIC ARM
Authors: Md Ghazaly Mariam , Teo Ting Huan , A/L Regeev Vivek , A/L Vijayan Kartikesu , Shin Hong Chong , Che Amran Aliza , Abdullah Zulkeflee , Md Ali Mohd Amran 
Published: July 2016

The objective of this paper is to design a controller which is able to control the output angle for an upper limb of a robotic arm, for precision motion and high speed response. The aim is to optimize the best controller for an upper limb robotic arm system for precision motion, in which improper motion will results in injuries/ fatality and loss of production in manufacturing system. In this research, a robotic arm prototype with a 1 degree-of-freedom (DOF) was designed and fabricated, in which the DC geared motor was implemented. Studies are carried out based on previous research to investigate the suitable type of controller. PID controller and fuzzy logic controller are chosen and compared in terms of their performances such as the steady-state error, settling time, rise time and overshoot. The equipment’s used are Micro-Box 2000/2000C, Cytron DC geared motor, motor driver circuit. Micro-Box module acts as the interface between hardware component and MATLAB R2009a. Open-loop simulations are carried out to obtain the transfer function of the motor and substituted into the system for further simulation analysis. Simulation for the uncompensated system is carried out to observe the close-loop system characteristic without the controller. After that, the close-loop point-to-point (PTP) trajectory control for simulations & experiments are carried out for the compensated systems using PID controller based on the Ziegler-Nichols frequency response method. Analyses are made based on the results obtained and the best type of controller is chosen for achieving precise motion control for the upper limb robotic arm. In this paper, the PID controller shows better performances compared to the Fuzzy Logic controller (FLC) with the steady state error of less than 0.010 and settling time of 0.5s; for the input reference of 150 respectively.
PALEOENVIRONMENT OF BROWN COAL FROM SANGATTA COAL MINES, EAST BORNEO, INDONESIA
Authors: Zetra Yulfi , B. Sosrowidjojo Imam , Burhan R. Y. Perry 
Published: July 2016

Organic geochemical studies on brown coal (lignite) located in Inul area were carried out, an area that is located in Sangatta coal mines, East Borneo, which is a part of the Balikpapan formation, aged as old as Middle Miocene to Late Miocene. Aliphatic hydrocarbon biomarker compounds which were identified by using the GC-MS analysis showed a presence of n-alkane (n-C12-n-C36) with bimodal distribution, which described the sources of organic compounds that originated from two different sources. These sources of organic compounds are phytoplankton, zooplankton and higher plants terrestrial. The Pr/Ph ratio of 1.3, the dominance of C31-homohopane and a high ratio of Tm/Ts indicated that the process of peat depositions took place in an oxic environment. The existence of hopanoid contents showed that there were dominant activities of microbes and biolipids organic compounds such as bb-hopane and hop-17(21)-ene inside the samples of olean-12-ene and a-cadinene, which inidicated that they are organic compounds that came from higher plants such as Angiosperm and immature coals. The existence of 24-ethylcholestene and 5b-cholest-24-ene found in the coal samples, which are categorised as steranes, also indicated a low level of carbonization from the coal itself.
Role of astrocyte–synapse interactions in CNS disorders
Authors: Blanco‐Suárez Elena , Caldwell Alison L. M. , Allen Nicola J. 
Published: July 2016

AbstractAstrocytes comprise half of the cells in the brain. Although astrocytes have traditionally been described as playing a supportive role for neurons, they have recently been recognized as active participants in the development and plasticity of dendritic spines and synapses. Astrocytes can eliminate dendritic spines, induce synapse formation, and regulate neurotransmission and plasticity. Dendritic spine and synapse impairments are features of many neurological disorders, including autism spectrum disorder, schizophrenia, and Alzheimer's disease. In this review we will present evidence from multiple neurological disorders demonstrating that changes in astrocyte–synapse interaction contribute to the pathologies. Genomic analysis has connected altered astrocytic gene expression with synaptic deficits in a number of neurological disorders. Alterations in astrocyte‐secreted factors have been implicated in the neuronal morphology and synaptic changes seen in neurodevelopmental disorders, while alteration in astrocytic glutamate uptake is a core feature of multiple neurodegenerative disorders. This evidence clearly demonstrates that maintaining astrocyte–synapse interaction is crucial for normal central nervous system functioning. Obtaining a better understanding of the role of astrocytes at synapses in health and disease will provide a new avenue for future therapeutic targeting.
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In Vitro
Exposure to PC-1005 and Cervicovaginal Lavage Fluid from Women Vaginally Administered PC-1005 Inhibits HIV-1 and HSV-2 Infection in Human Cervical Mucosa
Authors: Villegas Guillermo , Calenda Giulia , Zhang Shimin , Mizenina Olga , Kleinbeck Kyle , Cooney Michael L. , Hoesley Craig J. , Creasy George W. , Friedland Barbara , Fernández-Romero José A. , Zydowsky Thomas M. , Teleshova Natalia 
Published: July 2016

ABSTRACT

Our recent phase 1 trial demonstrated that PC-1005 gel containing 50 μM MIV-150, 14 mM zinc acetate dihydrate, and carrageenan (CG) applied daily vaginally for 14 days is safe and well tolerated. Importantly, cervicovaginal lavage fluid samples (CVLs) collected 4 or 24 h after the last gel application inhibited HIV-1 and human papillomavirus (HPV) in cell-based assays in a dose-dependent manner (MIV-150 for HIV-1 and CG for HPV). Herein we aimed to determine the anti-HIV and anti-herpes simplex virus 2 (anti-HSV-2) activity of PC-1005 in human cervical explants after
in vitro
exposure to the gel and to CVLs from participants in the phase 1 trial. Single HIV-1
BaL
infection and HIV-1
BaL
–HSV-2 coinfection explant models were utilized. Coinfection with HSV-2 enhanced tissue HIV-1
BaL
infection.
In vitro
exposure to PC-1005 protected cervical mucosa against HIV-1
BaL
(up to a 1:300 dilution) in single-challenge and cochallenge models. CG gel (PC-525) provided some barrier effect against HIV-1
BaL
at the 1:100 dilution in a single-challenge model but not in the cochallenge model. Both PC-1005 and PC-525 at the 1:100 dilution inhibited HSV-2 infection, pointing to a CG-mediated protection. MIV-150 and CG in CVLs inhibited HIV (single-challenge or cochallenge models) and HSV-2 infections in explants in a dose-dependent manner (
P
< 0.05). Stronger inhibition of HIV-1 infection by CVLs collected 4 h after the last gel administration was observed compared to infection detected in the presence of baseline CVLs. The anti-HIV and anti-HSV-2 activity of PC-1005 gel
in vitro
and CVLs in human ectocervical explants supports the further development of PC-1005 gel as a broad-spectrum on-demand microbicide.
Aspergillus fumigatus Intrinsic Fluconazole Resistance Is Due to the Naturally Occurring T301I Substitution in Cyp51Ap
Authors: Leonardelli Florencia , Macedo Daiana , Dudiuk Catiana , Cabeza Matias S. , Gamarra Soledad , Garcia-Effron Guillermo 
Published: July 2016

ABSTRACT

Aspergillus fumigatus
intrinsic fluconazole resistance has been demonstrated to be linked to the
CYP51A
gene, although the precise molecular mechanism has not been elucidated yet. Comparisons between
A. fumigatus
Cyp51Ap and
Candida albicans
Erg11p sequences showed differences in amino acid residues already associated with fluconazole resistance in
C. albicans
. The aim of this study was to analyze the role of the natural polymorphism I301 in
Aspergillus fumigatus
Cyp51Ap in the intrinsic fluconazole resistance phenotype of this pathogen. The I301 residue in
A. fumigatus
Cyp51Ap was replaced with a threonine (analogue to T315 at
Candida albicans
fluconazole-susceptible Erg11p) by changing one single nucleotide in the
CYP51A
gene. Also, a
CYP51A
knockout strain was obtained using the same parental strain. Both mutants' antifungal susceptibilities were tested. The I301T mutant exhibited a lower level of resistance to fluconazole (MIC, 20 μg/ml) than the parental strain (MIC, 640 μg/ml), while no changes in MIC were observed for other azole- and non-azole-based drugs. These data strongly implicate the
A. fumigatus
Cyp51Ap I301 residue in the intrinsic resistance to fluconazole.
Broad-Spectrum Antimicrobial Effects of Photocatalysis Using Titanium Dioxide Nanoparticles Are Strongly Potentiated by Addition of Potassium Iodide
Authors: Huang Ying-Ying , Choi Hwanjun , Kushida Yu , Bhayana Brijesh , Wang Yuguang , Hamblin Michael R. 
Published: July 2016

ABSTRACT

Photocatalysis describes the excitation of titanium dioxide nanoparticles (a wide-band gap semiconductor) by UVA light to produce reactive oxygen species (ROS) that can destroy many organic molecules. This photocatalysis process is used for environmental remediation, while antimicrobial photocatalysis can kill many classes of microorganisms and can be used to sterilize water and surfaces and possibly to treat infections. Here we show that addition of the nontoxic inorganic salt potassium iodide to TiO
2
(P25) excited by UVA potentiated the killing of Gram-positive bacteria, Gram-negative bacteria, and fungi by up to 6 logs. The microbial killing depended on the concentration of TiO
2
, the fluence of UVA light, and the concentration of KI (the best effect was at 100 mM). There was formation of long-lived antimicrobial species (probably hypoiodite and iodine) in the reaction mixture (detected by adding bacteria after light), but short-lived antibacterial reactive species (bacteria present during light) produced more killing. Fluorescent probes for ROS (hydroxyl radical and singlet oxygen) were quenched by iodide. Tri-iodide (which has a peak at 350 nm and a blue product with starch) was produced by TiO
2
-UVA-KI but was much reduced when methicillin-resistant
Staphylococcus aureus
(MRSA) cells were also present. The model tyrosine substrate
N
-acetyl tyrosine ethyl ester was iodinated in a light dose-dependent manner. We conclude that UVA-excited TiO
2
in the presence of iodide produces reactive iodine intermediates during illumination that kill microbial cells and long-lived oxidized iodine products that kill after light has ended.
Rifamycin Resistance in Clostridium difficile Is Generally Associated with a Low Fitness Burden
Authors: Dang Uyen T. , Zamora Idalia , Hevener Kirk E. , Adhikari Sudip , Wu Xiaoqian , Hurdle Julian G. 
Published: July 2016

ABSTRACT

We characterized clinically occurring and novel mutations in the β subunit of RNA polymerase in
Clostridium difficile
(
Cd
RpoB), conferring rifamycin (including rifaximin) resistance. The Arg
505
Lys substitution did not impose an
in vitro
fitness cost, which may be one reason for its dominance among rifamycin-resistant clinical isolates. These observations were supported through the structural modeling of
Cd
RpoB. In general, most mutations lacked
in vitro
fitness costs, suggesting that rifamycin resistance may in some cases persist in the clinic.
Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of the Parasite
Authors: Stanisic Danielle I. , Gerrard John , Fink James , Griffin Paul M. , Liu Xue Q. , Sundac Lana , Sekuloski Silvana , Rodriguez Ingrid B. , Pingnet Jolien , Yang Yuedong , Zhou Yaoqi , Trenholme Katharine R. , Wang Claire Y. T. , Hackett Hazel , Chan Jo-Anne A. , Langer Christine , Hanssen Eric , Hoffman Stephen L. , Beeson James G. , McCarthy James S. , Good Michael F. 
Published: July 2016

ABSTRACTPlasmodium falciparumis the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-gradeP. falciparumparasites (NF54, 7G8, and 3D7B) andex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants forin vitrocharacterization. All parasites were infectivein vivo. However, infectivity of NF54 was dramatically reduced.In vitrocharacterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggestingP. falciparumerythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence.
A Combined Computational and Genetic Approach Uncovers Network Interactions of the Cyanobacterial Circadian Clock
Authors: Boyd Joseph S. , Cheng Ryan R. , Paddock Mark L. , Sancar Cigdem , Morcos Faruck , Golden Susan S. 
Published: July 2016

ABSTRACT

Two-component systems (TCS) that employ histidine kinases (HK) and response regulators (RR) are critical mediators of cellular signaling in bacteria. In the model cyanobacterium
Synechococcus elongatus
PCC 7942, TCSs control global rhythms of transcription that reflect an integration of time information from the circadian clock with a variety of cellular and environmental inputs. The HK CikA and the SasA/RpaA TCS transduce time information from the circadian oscillator to modulate downstream cellular processes. Despite immense progress in understanding of the circadian clock itself, many of the connections between the clock and other cellular signaling systems have remained enigmatic. To narrow the search for additional TCS components that connect to the clock, we utilized direct-coupling analysis (DCA), a statistical analysis of covariant residues among related amino acid sequences, to infer coevolution of new and known clock TCS components. DCA revealed a high degree of interaction specificity between SasA and CikA with RpaA, as expected, but also with the phosphate-responsive response regulator SphR. Coevolutionary analysis also predicted strong specificity between RpaA and a previously undescribed kinase, HK0480 (herein CikB). A knockout of the gene for CikB (
cikB
) in a
sasA cikA
null background eliminated the RpaA phosphorylation and RpaA-controlled transcription that is otherwise present in that background and suppressed cell elongation, supporting the notion that CikB is an interactor with RpaA and the clock network. This study demonstrates the power of DCA to identify subnetworks and key interactions in signaling pathways and of combinatorial mutagenesis to explore the phenotypic consequences. Such a combined strategy is broadly applicable to other prokaryotic systems.

IMPORTANCE
Signaling networks are complex and extensive, comprising multiple integrated pathways that respond to cellular and environmental cues. A TCS interaction model, based on DCA, independently confirmed known interactions and revealed a core set of subnetworks within the larger HK-RR set. We validated high-scoring candidate proteins via combinatorial genetics, demonstrating that DCA can be utilized to reduce the search space of complex protein networks and to infer undiscovered specific interactions for signaling proteins
in vivo
. Significantly, new interactions that link circadian response to cell division and fitness in a light/dark cycle were uncovered. The combined analysis also uncovered a more basic core clock, illustrating the synergy and applicability of a combined computational and genetic approach for investigating prokaryotic signaling networks.
Analyzing Neisseria gonorrhoeae Pilin Antigenic Variation Using 454 Sequencing Technology
Authors: Rotman Ella , Webber David M. , Seifert H. Steven 
Published: July 2016

ABSTRACT

Many pathogens use homologous recombination to vary surface antigens in order to avoid immune surveillance.
Neisseria gonorrhoeae
, the bacterium responsible for the sexually transmitted infection gonorrhea, achieves this in part by changing the sequence of the major subunit of the type IV pilus in a process termed pilin antigenic variation (Av). The
N. gonorrhoeae
chromosome contains one expression locus (
pilE
) and many promoterless, partial-coding silent copies (
pilS
) that act as reservoirs for variant pilin information. Pilin Av occurs by high-frequency gene conversion reactions, which transfer
pilS
sequences into the
pilE
locus. We have developed a 454 sequencing-based assay to analyze the frequency and characteristics of pilin Av that allows a more robust analysis of pilin Av than previous assays. We used this assay to analyze mutations and conditions previously shown to affect pilin Av, confirming many but not all of the previously reported phenotypes. We show that mutations or conditions that cause growth defects can result in Av phenotypes when analyzed by phase variation-based assays. Adapting the 454 sequencing to analyze pilin Av demonstrates the utility of this technology to analyze any diversity generation system that uses recombination to develop biological diversity.

IMPORTANCE
Measuring and analyzing complex recombination-based systems constitute a major barrier to understanding the mechanisms used to generate diversity. We have analyzed the contributions of many gonococcal mutations or conditions to the process of pilin antigenic variation.
Primary and Secondary Sequence Structure Requirements for Recognition and Discrimination of Target RNAs by Pseudomonas aeruginosa RsmA and RsmF
Authors: Schulmeyer Kayley H. , Diaz Manisha R. , Bair Thomas B. , Sanders Wes , Gode Cindy J. , Laederach Alain , Wolfgang Matthew C. , Yahr Timothy L. 
Published: July 2016

ABSTRACT

CsrA family RNA-binding proteins are widely distributed in bacteria and regulate gene expression at the posttranscriptional level.
Pseudomonas aeruginosa
has a canonical member of the CsrA family (RsmA) and a novel, structurally distinct variant (RsmF). To better understand RsmF binding properties, we performed parallel systematic evolution of ligands by exponential enrichment (SELEX) experiments for RsmA and RsmF. The initial target library consisted of 62-nucleotide (nt) RNA transcripts with central cores randomized at 15 sequential positions. Most targets selected by RsmA and RsmF were the expected size and shared a common consensus sequence (CANGGAYG) that was positioned in a hexaloop region of the stem-loop structure. RsmA and RsmF also selected for longer targets (≥96 nt) that were likely generated by rare PCR errors. Most of the long targets contained two consensus-binding sites. Representative short (single consensus site) and long (two consensus sites) targets were tested for RsmA and RsmF binding. Whereas RsmA bound the short targets with high affinity, RsmF was unable to bind the same targets. RsmA and RsmF both bound the long targets. Mutation of either consensus GGA site in the long targets reduced or eliminated RsmF binding, suggesting a requirement for two tandem binding sites. Conversely, RsmA bound long targets containing only a single GGA site with unaltered affinity. The RsmF requirement for two binding sites was confirmed with
tssA1
, an
in vivo
regulatory target of RsmA and RsmF. Our findings suggest that RsmF binding requires two GGA-containing sites, while RsmA binding requirements are less stringent.

IMPORTANCE
The CsrA family of RNA-binding proteins is widely conserved in bacteria and plays important roles in the posttranscriptional regulation of protein synthesis.
P. aeruginosa
has two CsrA proteins, RsmA and RsmF. Although RsmA and RsmF share a few RNA targets, RsmF is unable to bind to other targets recognized by RsmA. The goal of the present study was to better understand the basis for differential binding by RsmF. Our data indicate that RsmF binding requires target RNAs with two consensus-binding sites, while RsmA recognizes targets with just a single binding site. This information should prove useful to future efforts to define the RsmF regulon and its contribution to
P. aeruginosa
physiology and virulence.
Shutdown of HIV-1 Transcription in T Cells by Nullbasic, a Mutant Tat Protein
Authors: Jin Hongping , Li Dongsheng , Sivakumaran Haran , Lor Mary , Rustanti Lina , Cloonan Nicole , Wani Shivangi , Harrich David 
Published: July 2016

ABSTRACT
Nullbasic is a derivative of the HIV-1 transactivator of transcription (Tat) protein that strongly inhibits HIV-1 replication in lymphocytes. Here we show that lentiviral vectors that constitutively express a Nullbasic-ZsGreen1 (NB-ZSG1) fusion protein by the eEF1α promoter led to robust long-term inhibition of HIV-1 replication in Jurkat cells. Although Jurkat-NB-ZSG1 cells were infected by HIV-1, no virus production could be detected and addition of phorbol ester 12-myristate 13-acetate (PMA) and JQ1 had no effect, while suberanilohydroxamic acid (SAHA) modestly stimulated virus production but at levels 300-fold lower than those seen in HIV-1-infected Jurkat-ZSG1 cells. Virus replication was not recovered by coculture of HIV-1-infected Jurkat-NB-ZSG1 cells with uninfected Jurkat cells. Latently infected Jurkat latent 6.3 and ACH2 cells treated with latency-reversing agents produced measurable viral capsid (CA), but little or none was made when they expressed NB-ZSG1. When Jurkat cells chronically infected with HIV-1 were transduced with lentiviral virus-like particles conveying NB-ZSG1, a >3-log reduction in CA production was observed. Addition of PMA increased virus CA production but at levels 500-fold lower than those seen in nontransduced Jurkat cells. Transcriptome sequencing analysis confirmed that HIV-1 mRNA was strongly inhibited by NB-ZSG1 but indicated that full-length viral mRNA was made. Analysis of HIV-1-infected Jurkat cells expressing NB-ZSG1 by chromatin immunoprecipitation assays indicated that recruitment of RNA polymerase II (RNAPII) and histone 3 lysine 9 acetylation were inhibited. The reduction of HIV-1 promoter-associated RNAPII and epigenetic changes in viral nucleosomes indicate that Nullbasic can inhibit HIV-1 replication by enforcing viral silencing in cells.

IMPORTANCE
HIV-1 infection is effectively controlled by antiviral therapy that inhibits virus replication and reduces measurable viral loads in patients below detectable levels. However, therapy interruption leads to viral rebound due to latently infected cells that serve as a source of continued viral infection. Interest in strategies leading to a functional cure of HIV infection by permanent viral suppression, which may be achievable, is growing. Here we show that a mutant form of the HIV-1 Tat protein, referred to as Nullbasic, can inhibit HIV-1 transcription in infected Jurkat T cell to undetectable levels. Analysis shows that Nullbasic alters the epigenetic state of the HIV-1 long terminal repeat promoter, inhibiting its association with RNA polymerase II. This study indicates that key cellular proteins and pathways targeted here can silence HIV-1 transcription. Further elucidation could lead to functional-cure strategies by suppression of HIV transcription, which may be achievable by a pharmacological method.