bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboxyl Analogue of Mutacin 1140, a Scaffold for Lead Antibacterial Discovery
Authors: Escano Jerome , Ravichandran Akshaya , Salamat Bita , Smith Leif 
Published: May 2017

ABSTRACT

Mutacin 1140 belongs to the epidermin group of lantibiotics. Epidermin class lantibiotics are ribosomally synthesized and posttranslationally modified antibiotics with potent activity against Gram-positive bacteria. In particular, this class is effective at targeting drug-resistant
Streptococcus pneumoniae
, methicillin-resistant
Staphylococcus aureus
(MRSA),
Mycobacterium tuberculosis
, and
Clostridium difficile
. A C-terminal
S
-[(Z)-2-aminovinyl]-
d
-cysteine (AviCys) residue is derived from a decarboxylation of a terminal cysteine that is involved in lanthionine ring formation. Studies on mutacin 1140 have revealed new insight into the structural importance of the C-terminal AviCys residue. A C-terminal carboxyl analogue of mutacin 1140 was engineered. Capping the C-terminal carboxyl group with a primary amine restores bioactivity and affords a novel opportunity to synthesize new analogues. A C-terminal fluorescein-labeled mutacin 1140 analogue traps lipid II into a large lipid II lantibiotic complex, similar to that observed
in vivo
for the lantibiotic nisin. A C-terminal carboxyl analogue of mutacin 1140 competitively inhibits the activity of native mutacin 1140 and nisin. The presence of a C-terminal carboxyl group prevents the formation of the large lipid II lantibiotic complexes but does not prevent the binding of the lantibiotic to lipid II.

IMPORTANCE
This study addressed the importance of the C-terminal
S
-[(Z)-2-aminovinyl]-
d
-cysteine (AviCys) residue for antibacterial activity. We have learned that the posttranslational modification for making the AviCys residue is presumably important for the lateral assembly mechanism of activity that traps lipid II into a large complex. The C-terminal carboxyl analogue of this class of lantibiotics is agreeable to the addition of a wide variety of substrates. The addition of fluorescein enabled
in vivo
visualization of the epidermin class of lantibiotics in action. These results are significant because, as we demonstrate, the presence of the AviCys residue is not essential for bioactivity, but, more importantly, the removal of the carboxyl group is essential. The ability to make a C-terminal carboxyl analogue that is modifiable will facilitate the synthesis of novel analogues of the epidermin class of lantibiotics that can be developed for new applications.
RpoN (σ
54
) Is Required for Floc Formation but Not for Extracellular Polysaccharide Biosynthesis in a Floc-Forming Aquincola tertiaricarbonis Strain
Authors: Yu Dianzhen , Xia Ming , Zhang Liping , Song Yulong , Duan You , Yuan Tong , Yao Minjie , Wu Liyou , Tian Chunyuan , Wu Zhenbin , Li Xiangzhen , Zhou Jizhong , Qiu Dongru 
Published: May 2017

ABSTRACT

Some bacteria are capable of forming flocs, in which bacterial cells become self-flocculated by secreted extracellular polysaccharides and other biopolymers. The floc-forming bacteria play a central role in activated sludge, which has been widely utilized for the treatment of municipal sewage and industrial wastewater. Here, we use a floc-forming bacterium,
Aquincola
tertiaricarbonis
RN12, as a model to explore the biosynthesis of extracellular polysaccharides and the regulation of floc formation. A large gene cluster for exopolysaccharide biosynthesis and a gene encoding the alternative sigma factor RpoN1, one of the four paralogues, have been identified in floc formation-deficient mutants generated by transposon mutagenesis, and the gene functions have been further confirmed by genetic complementation analyses. Interestingly, the biosynthesis of exopolysaccharides remained in the
rpoN1
-disrupted flocculation-defective mutants, but most of the exopolysaccharides were secreted and released rather than bound to the cells. Furthermore, the expression of exopolysaccharide biosynthesis genes seemed not to be regulated by RpoN1. Taken together, our results indicate that RpoN1 may play a role in regulating the expression of a certain gene(s) involved in the self-flocculation of bacterial cells but not in the biosynthesis and secretion of exopolysaccharides required for floc formation.

IMPORTANCE
Floc formation confers bacterial resistance to predation of protozoa and plays a central role in the widely used activated sludge process. In this study, we not only identified a large gene cluster for biosynthesis of extracellular polysaccharides but also identified four
rpoN
paralogues, one of which (
rpoN1
) is required for floc formation in
A. tertiaricarbonis
RN12. In addition, this RpoN sigma factor regulates the transcription of genes involved in biofilm formation and swarming motility, as previously shown in other bacteria. However, this RpoN paralogue is not required for the biosynthesis of exopolysaccharides, which are released and dissolved into culture broth by the
rpoN1
mutant rather than remaining tightly bound to cells, as observed during the flocculation of the wild-type strain. These results indicate that floc formation is a regulated complex process, and other yet-to-be identified RpoN1-dependent factors are involved in self-flocculation of bacterial cells via exopolysaccharides and/or other biopolymers.
Sodium Lactate Negatively Regulates Shewanella putrefaciens CN32 Biofilm Formation via a Three-Component Regulatory System (LrbS-LrbA-LrbR)
Authors: Liu Cong , Yang Jinshui , Liu Liang , Li Baozhen , Yuan Hongli , Liu Weijie 
Published: May 2017

ABSTRACT

The capability of biofilm formation has a major impact on the industrial and biotechnological applications of
Shewanella putrefaciens
CN32. However, the detailed regulatory mechanisms underlying biofilm formation in this strain remain largely unknown. In the present report, we describe a three-component regulatory system which negatively regulates the biofilm formation of
S. putrefaciens
CN32. This system consists of a histidine kinase LrbS (Sputcn32_0303) and two cognate response regulators, including a transcription factor, LrbA (Sputcn32_0304), and a phosphodiesterase, LrbR (Sputcn32_0305). LrbS responds to the signal of the carbon source sodium lactate and subsequently activates LrbA. The activated LrbA then promotes the expression of
lrbR
, the gene for the other response regulator. The bis-(3′-5′)-cyclic dimeric GMP (c-di-GMP) phosphodiesterase LrbR, containing an EAL domain, decreases the concentration of intracellular c-di-GMP, thereby negatively regulating biofilm formation. In summary, the carbon source sodium lactate acts as a signal molecule that regulates biofilm formation via a three-component regulatory system (LrbS-LrbA-LrbR) in
S. putrefaciens
CN32.

IMPORTANCE
Biofilm formation is a significant capability used by some bacteria to survive in adverse environments. Numerous environmental factors can affect biofilm formation through different signal transduction pathways. Carbon sources are critical nutrients for bacterial growth, and their concentrations and types significantly influence the biomass and structure of biofilms. However, knowledge about the underlying mechanism of biofilm formation regulation by carbon source is still limited. This work elucidates a modulation pattern of biofilm formation negatively regulated by sodium lactate as a carbon source via a three-component regulatory system in
S. putrefaciens
CN32, which may serve as a good example for studying how the carbon sources impact biofilm development in other bacteria.
Conjunctival lymphangiectasia associated with classic Fabry disease
Authors: Sivley Melanie D , Wallace Eric L , Warnock David G , Benjamin William J 
Published: May 2017

BackgroundFabry disease (FD) is a treatable multisystem disease caused by a defect in the alpha-galactosidase gene. Ocular signs of FD, including corneal verticillata, are among the earliest diagnostic findings. Conjunctival lymphangiectasia (CL) has not previously been associated with FD.MethodsWe examined the eyes of a cohort of 13 adult patients, eight men and five women, with documented classic FD, all treated with enzyme replacement therapy (ERT) at the University of Alabama at Birmingham between February 2014 and April 2015. The average age was 48 years with a range of 35–55 years for men and 21–71 years for women. The mean duration of ERT was 8.4 years (men 8.9 years, women 7.6 years) with a range of 4–14 years. Classical Fabry mutations included Q283X, R227X, W236X and W277X. A high resolution Haag-Streit BQ-900 slit lamp with EyeCap imaging system was used to record conjunctival images.ResultsCL was observed in 11 of the 13 patients (85%) despite long-term ERT. Clinical presentations included single cysts, beaded dilatations and areas of conjunctival oedema. Lesions were located within 6 mm of the corneal limbus. Ten of the 13 subjects (77%) had Fabry-related cataracts and all 13 demonstrated bilateral corneal verticillata. Twelve of the 13 patients had evidence of dry eye, 9 of whom were symptomatic, and 10 had peripheral lymphoedema.ConclusionCL represents a common but under-recognised ocular manifestation of FD, which persists despite ERT, and is often accompanied by peripheral lymphoedema and dry eye syndrome.
Comparison of two accelerometers for measuring physical activity and sedentary behaviour
Authors: Pfister Ted , Matthews Charles E , Wang Qinggang , Kopciuk Karen A , Courneya Kerry , Friedenreich Christine 
Published: May 2017

PurposeA central aspect of physical activity and sedentary behaviour research is accurate exposure assessment in the context of disease outcomes. The primary objectives of this study were to evaluate the convergent validity and test–retest reliability of the ActiGraph GT3X+ and activPAL3 accelerometers.MethodsParticipants from the Breast Cancer and Exercise Trial in Alberta (n=266) wore both devices concurrently during waking hours for 7 days. Summary measures of time (hours/day) for physical activity and sedentary behaviour were compared between devices using Student’s t-tests. Bland-Altman plots were used to assess or evaluate the mean differences and limits of agreement between monitors, and intraclass correlation coefficients (ICCs) were used to assess the test–retest reliability of two 7-day activity monitor administrations separated by 2 weeks (n=29).ResultsWhen comparing the ActiGraph Vector Magnitude (VM), which incorporates all three axes of movement (x, y, z), and the Vertical Axis (VT), which detects movement on the vertical or y-axis only, with the activPAL3, all measures of physical activity were statistically significantly different. The difference in measured time in sedentary behaviour was not statistically significant different when comparing the activPAL3 and ActiGraph (VT) estimates (p=0.47) but was statistically significant different for activPAL3 compared with ActiGraph (VM) (p<0.001). ICCs were high and consistent for each method across all behaviours, ranging from 0.87 to 0.93, with the exception of moderate activity and moderate-to-vigorous activity by the ActiGraph (VT) at 0.66 and 0.67, respectively.ConclusionDespite small mean differences and comparable recordings by both devices at the group level, the precision of estimates between methods was low with wide limits of agreement, suggesting these devices may not be used interchangeably for measuring physical activity and sedentary behaviour using common data reduction methods.
An exploration of patients’ experiences of participation in a randomised controlled trial of the Manchester Acute Coronary Syndromes (MACS) decision rule
Authors: van den Berg Patricia , Kendal Sarah , Alderson Helen V , Body Richard 
Published: May 2017

BackgroundAs an important part of a pilot study to determine the feasibility of a large randomised controlled trial (RCT) comparing use of the Manchester Acute Coronary Syndromes (MACS) decision rule with standard care, we aimed to explore patient attitudes and potential barriers to participation in a trial of this nature.MethodsWe conducted a qualitative study nested within a pilot RCT comparing use of the MACS rule (which could enable some patients with chest pain to be discharged earlier) with standard care. Semi-structured interviews with consenting participants were conducted with reference to a bespoke topic guide. Interviews were audio recorded, transcribed verbatim and analysed using the Framework method with an inductive approach.ResultsThe 10 interviewees expressed that participation in the trial was generally acceptable. All but one recommended participation to others. Participants who were in pain or anxious at the time of arrival reported that the initial invitation to participate in the trial was sometimes made too early. The approach was welcome, providing they had been given time to settle. Interviewees welcomed the opportunity that trial participation offered for them to play a more active role in their healthcare and to reduce unnecessary waiting time. Participants appeared to like the fact that participation in the trial might mean they could return home sooner and welcomed the provision of follow-up. Although several participants described being generally sceptical of medical research, they were amenable to participation in this trial. This appears to be because they agreed with the need for research in this field and perceived the intervention as non-invasive.ConclusionsPatients were positive about their participation in this RCT comparing the MACS rule with standard care. A number of areas for improving trial design were identified and should be considered in the planning of future large trials.Trial registrationISRCTN 86818215Research ethics committee reference13/NW/0081UKCRN registration ID14334
Evaluating the pictorial warnings on tobacco products in Arabian Gulf countries against other international pictorial warnings
Authors: BinDhim Nasser F , McGeechan Kevin , Alanazi Anwar K T , Alanazi Hossam M S , Alanazi Sasoun A J , Al-Hadlaq Solaiman M , Aljadhey Hisham , Alhawassi Tariq M , Alghamdi Nadia A , Shaman Ahmed M , Alquwayzani Meshari S , Basyouni Mada H 
Published: May 2017

BackgroundFew assessments of pictorial warnings (PWs) on cigarette packs implemented in Gulf Cooperation Council (GCC) countries have been done.MethodsThis article includes two cross-sectional studies. In Study 1, convenience samples of adults from the Kingdom of Saudi Arabia (n=111) and USA (n=115) participated in a consumer survey to rate a total of nine PWs from the GCC, Australia and the UK. Outcome measures were affective responses to PWs and concerns about smoking. In Study 2, tobacco control experts (n=14) from multiple countries rated the same PWs on a potential efficacy scale and completed one open-ended question about each. The PWs were altered to mask their country of origin. Analyses compared ranking on multiple outcomes and examined ratings by country of origin and by smoking status.ResultsIn the consumer survey, participants from both countries rated the PWs from GCC lower than PWs from other countries on the two measures. The mixed-model analysis showed significant differences between the PWs from Australia and those from the GCC and between the PWs from the UK and those from the GCC (p<0.001) in the consumer and expert samples. The experts’ comments about the PWs implemented in the GCC were negative overall and confirmed previously identified themes about effective PWs.ConclusionThis study shows PWs originating from the GCC had significantly lower ratings than those implemented in Australia and the UK. The GCC countries may need to re-evaluate the currently implemented PWs and update them periodically.
Suspected adverse events, 2015
Authors: Cooles S. , Diesel G. , Blenkinsop J. 
Published: May 2017

The following article has been produced by the pharmacovigilance unit at the Veterinary Medicines Directorate (VMD) to provide a summary of some of the results from its surveillance work carried out in 2015
Decrease in number of reports for food‐producing species
Increase in number of pet animal reports
Reports of dogs affected by medicines intended for large animals
A Closer Look at Variance Implementations In Modern Database Systems
Authors: Kamat Niranjan , Nandi Arnab 
Published: May 2017

Variance is a popular and often necessary component of aggregation queries. It is typically used as a secondary measure to ascertain statistical properties of the result such as its error. Yet, it is more expensive to compute than primary measures such as SUM, MEAN, and COUNT.
There exist numerous techniques to compute variance. While the definition of variance implies two passes overthe data, other mathematical formulations lead to a singlepass computation. Some single-pass formulations, however, can suffer from severe precision loss, especially for large datasets.
In this paper, we study variance implementations in various real-world systems and find that major database systems such as PostgreSQL and most likely System X, a major commercial closed-source database, use a representation that is efficient, but suffers from floating point precision loss resulting from catastrophic cancellation. We review literature over the past five decades on variance calculation in both the statistics and database communities, and summarize recommendations on implementing variance functions in various settings, such as approximate query processing and large-scale distributed aggregation. Interestingly, we recommend using the mathematical formula for computing variance if two passes over the data are acceptable due to its precision, parallelizability, and surprisingly computation speed.
SC-DCNN
Authors: Ren Ao , Li Zhe , Ding Caiwen , Qiu Qinru , Wang Yanzhi , Li Ji , Qian Xuehai , Yuan Bo 
Published: May 2017

With the recent advance of wearable devices and Internet of Things (IoTs), it becomes attractive to implement the Deep Convolutional Neural Networks (DCNNs) in embedded and portable systems. Currently, executing the software-based DCNNs requires high-performance servers, restricting the widespread deployment on embedded and mobile IoT devices. To overcome this obstacle, considerable research efforts have been made to develop highly-parallel and specialized DCNN accelerators using GPGPUs, FPGAs or ASICs.
Stochastic Computing (SC), which uses a bit-stream to represent a number within [-1, 1] by counting the number of ones in the bit-stream, has high potential for implementing DCNNs with high scalability and ultra-low hardware footprint. Since multiplications and additions can be calculated using AND gates and multiplexers in SC, significant reductions in power (energy) and hardware footprint can be achieved compared to the conventional binary arithmetic implementations. The tremendous savings in power (energy) and hardware resources allow immense design space for enhancing scalability and robustness for hardware DCNNs.

This paper presents SC-DCNN, the first comprehensive design and optimization framework of SC-based DCNNs, using a bottom-up approach. We first present the designs of function blocks that perform the basic operations in DCNN, including inner product, pooling, and activation function. Then we propose four designs of feature extraction blocks, which are in charge of extracting features from input feature maps, by connecting different basic function blocks with joint optimization. Moreover, the efficient weight storage methods are proposed to reduce the area and power (energy) consumption. Putting all together, with feature extraction blocks carefully selected, SC-DCNN is holistically optimized to minimize area and power (energy) consumption while maintaining high network accuracy. Experimental results demonstrate that the LeNet5 implemented in SC-DCNN consumes only 17
mm
2
area and 1.53 W power, achieves throughput of 781250 images/s, area efficiency of 45946 images/s/
mm
2
, and energy efficiency of 510734 images/J.
Nanoformulation of Olaparib Amplifies PARP Inhibition and Sensitizes PTEN/TP53-Deficient Prostate Cancer to Radiation
Authors: van de Ven Anne L. , Tangutoori Shifalika , Baldwin Paige , Qiao Ju , Gharagouzloo Codi , Seitzer Nina , Clohessy John G. , Makrigiorgos G. Mike , Cormack Robert , Pandolfi Pier Paolo , Sridhar Srinivas 
Published: May 2017

Abstract
The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage in tumors. Here we show that radiation-resistant cells and tumors derived from a Pten/Trp53-deficient mouse model of advanced prostate cancer are rendered radiation sensitive following treatment with NanoOlaparib, a lipid-based injectable nanoformulation of olaparib. This enhancement in radiosensitivity is accompanied by radiation dose-dependent changes in γ-H2AX expression and is specific to NanoOlaparib alone. In animals, twice-weekly intravenous administration of NanoOlaparib results in significant tumor growth inhibition, whereas previous studies of oral olaparib as monotherapy have shown no therapeutic efficacy. When NanoOlaparib is administered prior to radiation, a single dose of radiation is sufficient to triple the median mouse survival time compared to radiation only controls. Half of mice treated with NanoOlaparib + radiation achieved a complete response over the 13-week study duration. Using ferumoxytol as a surrogate nanoparticle, MRI studies revealed that NanoOlaparib enhances the intratumoral accumulation of systemically administered nanoparticles. NanoOlaparib-treated tumors showed up to 19-fold higher nanoparticle accumulation compared to untreated and radiation-only controls, suggesting that the in vivo efficacy of NanoOlaparib may be potentiated by its ability to enhance its own accumulation. Together, these data suggest that NanoOlaparib may be a promising new strategy for enhancing the radiosensitivity of radiation-resistant tumors lacking BRCA mutations, such as those with PTEN and TP53 deletions. Mol Cancer Ther; 16(7); 1279–89. ©2017 AACR.
Cardiometabolic Traits and Systolic Mechanics in the Community
Authors: Ho Jennifer E. , McCabe Elizabeth L. , Wang Thomas J. , Larson Martin G. , Levy Daniel , Tsao Connie , Aragam Jayashri , Mitchell Gary F. , Benjamin Emelia J. , Vasan Ramachandran S. , Cheng Susan 
Published: May 2017

Background—
Obesity and cardiometabolic dysfunction are associated with increased risk of heart failure and other cardiovascular diseases. We sought to examine the association of cardiometabolic traits with left ventricular (LV) cardiac mechanics. We hypothesized that specific obesity-related phenotypes are associated with distinct aspects of LV strain.

Methods and Results—

We evaluated the associations of obesity-related phenotypes, including central adiposity, diabetes mellitus, insulin resistance, and circulating adipokine concentrations with echocardiographic measures of LV mechanical function among participants of the Framingham Heart Study Offspring and Third Generation cohorts. Among 6231 participants, the mean age was 51±16 years, and 54% were women. Greater body mass index was associated with worse LV longitudinal strain, radial strain (apical view), and longitudinal synchrony (multivariable-adjusted
P
<0.0001). After accounting for body mass index, we found that central adiposity, as measured by waist circumference, was associated with worse global longitudinal strain and synchrony (
P
≤0.006). Measures of insulin resistance, dyslipidemia, and diabetes mellitus also were associated with distinct aspects of LV mechanical function. Circulating leptin concentrations were associated with global longitudinal and radial strain (apical view,
P
<0.0001), whereas no such association was found with leptin receptor, adiponectin, or C-reactive protein.

Conclusions—
Our findings highlight the association of central obesity and related cardiometabolic phenotypes above and beyond body mass index with subclinical measures of LV mechanical function. Interestingly, obesity-related traits were associated with distinct aspects of LV mechanics, underscoring potential differential effects along specific LV planes of deformation. These findings may shed light onto obesity-related cardiac remodeling and heart failure.